Clinical trial research is the cornerstone for successful advancement of medicine that provides hope for millions of people in the future. Full transparency in clinical trials may allow independent investigators to evaluate study designs, perform additional analysis of data, and potentially eliminate duplicate studies. Current regulatory system and publishers rely on investigators and pharmaceutical industries for complete and accurate reporting of results from completed clinical trials. Legislation seems to be the only way to enforce mandatory disclosure of results. The Trial and Experimental Studies Transparency (TEST) Act of 2012 was introduced to the legislators in the United States to promote greater transparency in research industry. Public safety and advancement of science are the driving forces for the proposed policy change. The TEST Act may benefit the society and researchers; however, there are major concerns with participants' privacy and intellectual property protection. Copyright © 2014 Elsevier Inc. All rights reserved.
groups of ACT are individuals who have complex support needs due to for instance mental illness and/or substance abuse and for whom it is difficult to use mainstream support systems. The team consists not only of social support workers but also of a psychiatrist, a nurse and an addiction councilor......, and social workers with administrative authority from the social office and the job center. In the international research literature ACT has been shown in randomized controlled trials to be a very effective method in bringing individuals out of homelessness and into a stable housing situation. This study...... is based on quantitative outcome measurement in an intervention group of about 60 homeless individuals who through the program has received both a housing solution and support from the ACT-team. The study is not a randomized controlled trial as there is no control group. Furthermore qualitative interviews...
Bader, James D.; Vollmer, William M.; Shugars, Daniel A.; Gilbert, Gregg H.; Amaechi, Bennett T.; Brown, John P.; Laws, Reesa L.; Funkhouser, Kimberly A.; Makhija, Sonia K.; Ritter, André V.; Leo, Michael C.
Background Although caries is prevalent in adults, few preventive therapies have been tested in adult populations. This randomized clinical trial evaluated the effectiveness of xylitol lozenges in preventing caries in elevated caries-risk adults. Methods X-ACT was a three-site placebo-controlled randomized trial. Participants (n=691) ages 21–80 consumed five 1.0 g xylitol or placebo lozenges daily for 33 months. Clinical examinations occurred at baseline, 12, 24 and 33 months. Results Xylitol lozenges reduced the caries increment 11%. This reduction, which represented less than one-third of a surface per year, was not statistically significant. There was no indication of a dose-response effect. Conclusions Daily use of xylitol lozenges did not result in a statistically or clinically significant reduction in 33-month caries increment among elevated caries-risk adults. Clinical Implications These results suggest that xylitol used as a supplement in adults does not significantly reduce their caries experience. PMID:23283923
In December 1965, an experiment took place at The Independent Art Space in Copenhagen (Den Frie Kunstbygning). Short named POEX65, it was looking to create and activate POetry EXperiments across artistic genres and formats (thus, in essence, making a POetry EXposition). The POEX65 event framed many...... to be able to analyse the phenomena found at POEX65. Here I will use the notion of the ‘ontological theatre’ (Pickering), which, according to Pickering, is acted out in experimental art productions. The experiment could thus be seen as an ‘agency-realism’ – as an ‘act’ of relations across the aesthetics...
Full Text Available Abstract Background As the number of randomised controlled trials of medicines for children increases, it becomes progressively more important to understand the experiences of parents who are asked to enrol their child in a trial. This paper presents a narrative review of research evidence on parents' experiences of trial recruitment focussing on qualitative research, which allows them to articulate their views in their own words. Discussion Parents want to do their best for their children, and socially and legally their role is to care for and protect them yet the complexities of the medical and research context can challenge their fulfilment of this role. Parents are simultaneously responsible for their child and cherish this role yet they are dependent on others when their child becomes sick. They are keen to exercise responsibility for deciding to enter a child in a trial yet can be fearful of making the 'wrong' decision. They make judgements about the threat of the child's condition as well as the risks of the trial yet their interpretations often differ from those of medical and research experts. Individual pants will experience these and other complexities to a greater or lesser degree depending on their personal experiences and values, the medical situation of their child and the nature of the trial. Interactions at the time of trial recruitment offer scope for negotiating these complexities if practitioners have the flexibility to tailor discussions to the needs and situation of individual parents. In this way, parents may be helped to retain a sense that they have acted as good parents to their child whatever decision they make. Summary Discussing randomised controlled trials and gaining and providing informed consent is challenging. The unique position of parents in giving proxy consent for their child adds to this challenge. Recognition of the complexities parents face in making decisions about trials suggests lines for future
Shilling, Valerie; Young, Bridget
As the number of randomised controlled trials of medicines for children increases, it becomes progressively more important to understand the experiences of parents who are asked to enroll their child in a trial. This paper presents a narrative review of research evidence on parents' experiences of trial recruitment focussing on qualitative research, which allows them to articulate their views in their own words. Parents want to do their best for their children, and socially and legally their role is to care for and protect them yet the complexities of the medical and research context can challenge their fulfillment of this role. Parents are simultaneously responsible for their child and cherish this role yet they are dependent on others when their child becomes sick. They are keen to exercise responsibility for deciding to enter a child in a trial yet can be fearful of making the 'wrong' decision. They make judgements about the threat of the child's condition as well as the risks of the trial yet their interpretations often differ from those of medical and research experts. Individual parents will experience these and other complexities to a greater or lesser degree depending on their personal experiences and values, the medical situation of their child and the nature of the trial. Interactions at the time of trial recruitment offer scope for negotiating these complexities if practitioners have the flexibility to tailor discussions to the needs and situation of individual parents. In this way, parents may be helped to retain a sense that they have acted as good parents to their child whatever decision they make. Discussing randomised controlled trials and gaining and providing informed consent is challenging. The unique position of parents in giving proxy consent for their child adds to this challenge. Recognition of the complexities parents face in making decisions about trials suggests lines for future research on the conduct of trials, and ultimately, may help
Abstract. Long-acting reversible hormonal contraceptives are effective methods of birth control that provide contraception for an extended ... The World Health Organization (WHO) has online tools available .... trials and marketing experience.
Mathieu, Erin; Barratt, Alexandra; Carter, Stacy M; Jamtvedt, Gro
Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants' attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate). Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants' comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience - a perceived benefit - and a lack connectedness and understanding - a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet; security, privacy and confidentiality issues; perceived benefits and
Background Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants’ attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. Objective To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. Methods All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. Results 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate). Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants’ comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience – a perceived benefit – and a lack connectedness and understanding – a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet; security, privacy and
Full Text Available Abstract Background Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants’ attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. Objective To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. Methods All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. Results 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate. Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants’ comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience – a perceived benefit – and a lack connectedness and understanding – a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet
Amaechi Bennett T
Full Text Available Abstract Background Dental caries incidence in adults is similar to that in children and adolescents, but few caries preventive agents have been evaluated for effectiveness in adults populations. In addition, dentists direct fewer preventive services to their adult patients. Xylitol, an over-the-counter sweetener, has shown some potential as a caries preventive agent, but the evidence for its effectiveness is not yet conclusive and is based largely on studies in child populations. Methods/Design X-ACT is a three-year, multi-center, placebo controlled, double-blind, randomized clinical trial that tests the effects of daily use of xylitol lozenges versus placebo lozenges on the prevention of adult caries. The trial has randomized 691 participants (ages 21-80 to the two arms. The primary outcome is the increment of cavitated lesions. Discussion This trial should help resolve the overall issue of the effectiveness of xylitol in preventing caries by contributing evidence with a low risk of bias. Just as importantly, the trial will provide much-needed information about the effectiveness of a promising caries prevention agent in adults. An effective xylitol-based caries prevention intervention would represent an easily disseminated method to extend caries prevention to individuals not receiving caries preventive treatment in the dental office. Trial Registration ClinicalTrials.Gov NCT00393055
Mackay, Christine B; Antonelli, Kaitlyn R; Bruinooge, Suanna S; Saint Onge, Jarron M; Ellis, Shellie D
The Affordable Care Act (ACA) includes a mandate requiring most private health insurers to cover routine patient care costs for cancer clinical trial participation; however, the impact of this provision on cancer centers' efforts to accrue patients to clinical trials has not been well described. First, members of cancer research centers and community-based institutions (n = 252) were surveyed to assess the status of insurance denials, and then, a focused survey (n = 77) collected denial details. Univariate and multivariate analyses were used to examine associations between the receipt of denials and site characteristics. Overall, 62.7% of the initial survey respondents reported at least 1 insurance denial during 2014. Sites using a precertification process were 3.04 times more likely to experience denials (95% confidence interval, 1.55-5.99; P ≤ .001), and similar rates of denials were reported from sites located in states with preexisting clinical trial coverage laws versus states without them (82.3% vs 85.1%; χ = 50.7; P ≤ .001). Among the focused survey sites, academic centers reported denials more often than community sites (71.4% vs 46.4%). The failure of plans to cover trial participation was cited as the most common reason provided for denials (n = 33 [80.5%]), with nearly 80% of sites (n = 61) not receiving a coverage response from the insurer within 72 hours. Despite the ACA's mandate for most insurers to cover routine care costs for cancer clinical trial participation, denials and delays continue. Denials may continue because some insurers remain exempt from the law, or they may signal an implementation failure. Delays in coverage may affect patient participation in trials. Additional efforts to eliminate this barrier will be needed to achieve federal initiatives to double the pace of cancer research over the next 5 years. Future work should assess the law's effectiveness at the patient level to inform these efforts
Hubacher, David; Spector, Hannah; Monteith, Charles; Chen, Pai-Lien; Hart, Catherine
Measures of contraceptive effectiveness combine technology and user-related factors. Observational studies show higher effectiveness of long-acting reversible contraception compared with short-acting reversible contraception. Women who choose long-acting reversible contraception may differ in key ways from women who choose short-acting reversible contraception, and it may be these differences that are responsible for the high effectiveness of long-acting reversible contraception. Wider use of long-acting reversible contraception is recommended, but scientific evidence of acceptability and successful use is lacking in a population that typically opts for short-acting methods. The objective of the study was to reduce bias in measuring contraceptive effectiveness and better isolate the independent role that long-acting reversible contraception has in preventing unintended pregnancy relative to short-acting reversible contraception. We conducted a partially randomized patient preference trial and recruited women aged 18-29 years who were seeking a short-acting method (pills or injectable). Participants who agreed to randomization were assigned to 1 of 2 categories: long-acting reversible contraception or short-acting reversible contraception. Women who declined randomization but agreed to follow-up in the observational cohort chose their preferred method. Under randomization, participants chose a specific method in the category and received it for free, whereas participants in the preference cohort paid for the contraception in their usual fashion. Participants were followed up prospectively to measure primary outcomes of method continuation and unintended pregnancy at 12 months. Kaplan-Meier techniques were used to estimate method continuation probabilities. Intent-to-treat principles were applied after method initiation for comparing incidence of unintended pregnancy. We also measured acceptability in terms of level of happiness with the products. Of the 916
Full Text Available Abstract Background Half of all lower limb deep vein thrombi (DVT in symptomatic ambulatory patients are located in the distal (calf veins. While proximal disease warrants therapeutic anticoagulation to reduce the associated risks, distal DVT often goes untreated. However, a proportion of untreated distal disease will undoubtedly propagate or embolize. Concern also exists that untreated disease could lead to long-term post thrombotic changes. Currently, it is not possible to predict which distal thrombi will develop such complications. Whether these potential risks outweigh those associated with unrestricted anticoagulation remains unclear. The Anticoagulation of Calf Thrombosis (ACT trial aims to compare therapeutic anticoagulation against conservative management for patients with acute symptomatic distal deep vein thrombosis. Methods ACT is a pragmatic, open-label, randomized controlled trial. Adult patients diagnosed with acute distal DVT will be allocated to either therapeutic anticoagulation or conservative management. All patients will undergo 3 months of clinical and assessor blinded sonographic follow-up, followed by 2-year final review. The project will commence initially as an external pilot study, recruiting over a 16-month period at a single center to assess feasibility measures and clinical event rates. Primary outcome measures will assess feasibility endpoints. Secondary clinical outcomes will be collected to gather accurate data for the design of a definitive clinical trial and will include: (1 a composite endpoint combining thrombus propagation to the popliteal vein or above, development of symptomatic pulmonary embolism or sudden death attributable to venous thromboembolic disease; (2 the incidence of major and minor bleeding episodes; (3 the incidence of post-thrombotic leg syndrome at 2 years using a validated screening tool; and (4 the incidence of venous thromboembolism (VTE recurrence at 2 years. Discussion The ACT trial
Mansour, J K; Beaudry, J L; Lindsay, R C L
Eyewitness identification experiments typically involve a single trial: A participant views an event and subsequently makes a lineup decision. As compared to this single-trial paradigm, multiple-trial designs are more efficient, but significantly reduce ecological validity and may affect the strategies that participants use to make lineup decisions. We examined the effects of a number of forensically relevant variables (i.e., memory strength, type of disguise, degree of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376 lineup decisions). The rates of correct rejections and choosing (across both target-present and target-absent lineups) did not vary across the 24 trials, as reflected by main effects or interactions with trial number. Trial number had a significant but trivial quadratic effect on correct identifications (OR = 0.99) and interacted significantly, but again trivially, with disguise type (OR = 1.00). Trial number did not significantly influence participants' confidence in correct identifications, confidence in correct rejections, or confidence in target-absent selections. Thus, multiple-trial designs appear to have minimal effects on eyewitness accuracy, choosing, and confidence. Researchers should thus consider using multiple-trial designs for conducting eyewitness identification experiments.
McNay, Laura A; Tavel, Jorge A; Oseekey, Karen; McDermott, Cathy M; Mollerup, David; Bebchuk, Judith D
While accepted as serving an important function to safeguard human subjects, the process of obtaining regulatory approvals to conduct clinical trials is generally regarded as cumbersome and time-consuming. For large multinational trials, U.S. federally sponsored human subject research abroad involves specific U.S. regulatory requirements, in addition to those of the host country, that act as further hurdles. These requirements may include obtaining an Assurance of Protection for Human Subjects from the Office of Human Research Protection of the U.S. Department of Health and Human Services, maintaining specific Ethics Committee/Institutional Review Board (EC/IRB) composition, and incorporating mandated elements in informed consents, all of which may differ from local policies and guidelines. Specific examples of issues that led to delays in regulatory approvals for sites participating in the multinational clinical trial entitled Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) are presented here. While the goal of these requirements is to protect the rights and welfare of human subjects, they may create substantial delays and engender resentment over the notion of lack of respect for individual country sovereignty. Substudies within ESPRIT have been undertaken to obtain feedback from EC/IRB chairpersons, site personnel responsible for processing the required assurances, ESPRIT investigators, and study participants regarding aspects of current U.S. regulatory requirements related to human subject protection and ethical issues in multinational research. The purpose of these substudies is to compare the attitudes and experiences across countries regarding important ethical issues associated with conducting ESPRIT. One objective of the substudies is to gather additional insight to the impact of U.S. regulatory processes. Another is to help to inform the debate about how to best maximize the rights and welfare of clinical trial
Ihrke, Matthias; Behrendt, Jörg
In most psychological experiments, a randomized presentation of successive displays is crucial for the validity of the results. For some paradigms, this is not a trivial issue because trials are interdependent, e.g., priming paradigms. We present a software that automatically generates optimized trial sequences for (negative-) priming experiments. Our implementation is based on an optimization heuristic known as genetic algorithms that allows for an intuitive interpretation due to its similarity to natural evolution. The program features a graphical user interface that allows the user to generate trial sequences and to interactively improve them. The software is based on freely available software and is released under the GNU General Public License.
In this research the role of the RH in the comprehension of speech acts (or illocutionary force) was examined. Two split-screen experiments were conducted in which participants made lexical decisions for lateralized targets after reading a brief conversation remark. On one-half of the trials the target word named the speech act performed with the…
Huang, David T; Angus, Derek C; Chang, Chung-Chou H; Doi, Yohei; Fine, Michael J; Kellum, John A; Peck-Palmer, Octavia M; Pike, Francis; Weissfeld, Lisa A; Yabes, Jonathan; Yealy, Donald M
Overuse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns. The Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection. We describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation. ClinicalTrials.gov NCT02130986 . Registered May 1, 2014.
Acosta, Roberto J.; Larko, Jeffrey M.; Lagin, Alan R.
The Advanced Communication Technology Satellite (ACTS) is a key to reaching NASA's goal of developing high-risk, advanced communications technology using multiple frequency bands to support the nation's future communication needs. Using the multiple, dynamic hopping spot beams, and advanced on board switching and processing systems, ACTS will open a new era in communications satellite technology. One of the key technologies to be validated as part of the ACTS program is the multibeam antenna with rapidly reconfigurable hopping and fixed spot beam to serve users equipped with small-aperature terminals within the coverage areas. The proposed antenna technology experiments are designed to evaluate in-orbit ACTS multibeam antenna performance (radiation pattern, gain, cross pol levels, etc.).
Casey, Máire-Bríd; Smart, Keith; Segurado, Ricardo; Hearty, Conor; Gopal, Hari; Lowry, Damien; Flanagan, Dearbhail; McCracken, Lance; Doody, Catherine
purposeful sample of participants to explore patient experiences of both treatments. To our knowledge, this will be the first RCT to examine whether combining exercise with ACT produces greater benefit for patients with chronic pain, compared to a standalone supervised exercise programme. www.ClinicalTrials.gov, ID: NCT03050528 . Registered on 13 February 2017.
Nyaku, Amesika N; Kelly, Sean G; Taiwo, Babafemi O
Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.
Full Text Available Randomised controlled clinical trials are fundamental in medicine to develop new effective drugs and new therapeutic regimens and are the strength of evidence-based medicine. These studies allow us to avoid the repetition of misleading experiences that have been reported in the past, where drugs or associations were utilised without compelling evidence and ultimately proven to be ineffective. In recent years, randomised clinical trials have been conducted and concluded for many rare diseases, including idiopathic pulmonary fibrosis. However, clinical trials do not always reflect the real-life scenario. Patients selected for clinical trials present fewer comorbidities, they fall between certain age limits, and the severity of their disease is defined; therefore, they do not always reflect the whole of the population affected by a specific disease. These are the reasons why we also need data that mirror real-life experience. The limitations that these kind of studies present are always several and the studies should be interpreted with caution, although they can fill the important gap between efficacy and effectiveness. In this article, we will review the existing clinical data on real-life treatment of idiopathic pulmonary fibrosis.
Full Text Available Eva G Katz,1 Brett Hauber,2 Srihari Gopal,3 Angie Fairchild,2 Amy Pugh,4 Rachel B Weinstein,3 Bennett S Levitan3 1Janssen Research & Development, LLC, Raritan, NJ, 2RTI Health Solutions, Research Triangle Park, NC, 3Janssen Research & Development, LLC, Titusville, NJ, 4The University of California, San Francisco (UCSF, CA, USA Purpose: To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence.Methods: Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models.Results: Patients (N=214 and physicians (N=438 preferred complete improvement in positive symptoms (severe to none as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05, irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI] that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2–12.4, 20% nonadherent: 25.4% (95% CI: 21.0–29.9, and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1, nonadherent: the change in efficacy studied was
Masiello, C. A.; Gao, X.; Dugan, B.; Silberg, J. J.; Zygourakis, K.; Alvarez, P. J. J.
The biochar community is excellent at pointing to individual cases where biochar amendment has changed soil properties, with some studies showing significant improvements in crop yields, reduction in nutrient export, and remediation of pollutants. However, many studies exist which do not show improvements, and in some cases, studies clearly show detrimental outcomes. The next, crucial step in biochar science and engineering research will be to develop a process-based understanding of how biochar acts to improve soil properties. In particular, we need a better mechanistic understanding of how biochar sorbs and desorbs contaminants, how it interacts with soil water, and how it interacts with the soil microbial community. These mechanistic studies need to encompass processes that range from the nanometer to the kilometer scale. At the nanometer scale, we need a predictive model of how biochar will sorb and desorb hydrocarbons, nutrients, and toxic metals. At the micrometer scale we need models that explain biochar's effects on soil water, especially the plant-available fraction of soil water. The micrometer scale is also where mechanistic information is neeed about microbial processes. At the macroscale we need physical models to describe the landscape mobility of biochar, because biochar that washes away from fields can no longer provide crop benefits. To be most informative, biochar research should occur along a lab-greenhouse-field trial trajectory. Laboratory experiments should aim determine what mechanisms may act to control biochar-soil processes, and then greenhouse experiments can be used to test the significance of lab-derived mechanisms in short, highly replicated, controlled experiments. Once evidence of effect is determined from greenhouse experiments, field trials are merited. Field trials are the gold standard needed prior to full deployment, but results from field trials cannot be extrapolated to other field sites without the mechanistic backup provided
Grigg, M J; William, T; Dhanaraj, P; Menon, J; Barber, B E; von Seidlein, L; Rajahram, G; Price, R N; Anstey, N M; Yeo, T W
Introduction Malaria due to Plasmodium knowlesi is reported throughout South-East Asia, and is the commonest cause of it in Malaysia. P. knowlesi replicates every 24 h and can cause severe disease and death. Current 2010 WHO Malaria Treatment Guidelines have no recommendations for the optimal treatment of non-severe knowlesi malaria. Artemisinin-combination therapies (ACT) and chloroquine have each been successfully used to treat knowlesi malaria; however, the rapidity of parasite clearance has not been prospectively compared. Malaysia's national policy for malaria pre-elimination involves mandatory hospital admission for confirmed malaria cases with discharge only after two negative blood films; use of a more rapidly acting antimalarial agent would have health cost benefits. P. knowlesi is commonly microscopically misreported as P. malariae, P. falciparum or P. vivax, with a high proportion of the latter two species being chloroquine-resistant in Malaysia. A unified ACT-treatment protocol would provide effective blood stage malaria treatment for all Plasmodium species. Methods and analysis ACT KNOW, the first randomised controlled trial ever performed in knowlesi malaria, is a two-arm open-label trial with enrolments over a 2-year period at three district sites in Sabah, powered to show a difference in proportion of patients negative for malaria by microscopy at 24 h between treatment arms (clinicaltrials.gov #NCT01708876). Enrolments started in December 2012, with completion expected by September 2014. A total sample size of 228 is required to give 90% power (α 0.05) to determine the primary end point using intention-to-treat analysis. Secondary end points include parasite clearance time, rates of recurrent infection/treatment failure to day 42, gametocyte carriage throughout follow-up and rates of anaemia at day 28, as determined by survival analysis. Ethics and dissemination This study has been approved by relevant institutional ethics committees in
Werner, Anette; Uldbjerg, Niels; Zachariae, Robert; Wu, Chun Sen; Nohr, Ellen A
Childbirth is a demanding event in a woman's life. The aim of this study was to explore whether a brief intervention in the form of an antenatal course in self-hypnosis to ease childbirth could improve the childbirth experience. In a randomized, controlled, single-blinded trial, 1,222 healthy nulliparous women were allocated to one of three groups during pregnancy: A hypnosis group participating in three 1-hour sessions teaching self-hypnosis to ease childbirth, a relaxation group receiving three 1-hour lessons in various relaxation methods and Mindfulness, and a usual care group receiving ordinary antenatal care only. Wijmas Delivery Expectancy/Experience Questionnaire (W-DEQ) was used to measure the childbirth experience 6 weeks postpartum. The intention-to-treat analysis indicated that women in the hypnosis group experienced their childbirth as better compared with the other two groups (mean W-DEQ score of 42.9 in the Hypnosis group, 47.2 in the Relaxation group, and 47.5 in the Care as usual group (p = 0.01)). The tendency toward a better childbirth experience in the hypnosis group was also seen in subgroup analyses for mode of delivery and for levels of fear. In this large randomized controlled trial, a brief course in self-hypnosis improved the women's childbirth experience. © 2013, Copyright the Authors Journal compilation © 2013, Wiley Periodicals, Inc.
Williamson, Rebecca A; Meltzoff, Andrew N
Young children learn from others' examples, and they do so selectively. We examine whether the efficacy of prior experiences influences children's imitation. Thirty-six-month-olds had initial experience on a causal learning task either by performing the task themselves or by watching an adult perform it. The nature of the experience was manipulated such that the actor had either an easy or a difficult experience completing the task. Next, a second adult demonstrated an innovative technique for completing it. Children who had a difficult first-person experience, and those who had witnessed another person having difficulty, were significantly more likely to adopt and imitate the adult's innovation than those who had or witnessed an easy experience. Children who observed another were also more likely to imitate than were those who had the initial experience themselves. Imitation is influenced by prior experience, both when it is obtained through one's own hands-on motor manipulation and when it derives from observing the acts of others.
Full Text Available ... medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key research tool for ... and Usage No FEAR Act Grants and Funding Customer Service/Center for Health Information Email Alerts Jobs ...
Full Text Available Abstract Background The internet is frequently used to share experiences of health and illness, but this phenomenon has not been harnessed as an intervention to achieve health behaviour change. The aim of this study was to determine the feasibility of a randomised trial assessing the effects of a novel, experience-based website as a smoking cessation intervention. The secondary aim was to measure the potential impact on smoking behaviour of both the intervention and a comparator website. Methods A feasibility randomised controlled single-blind trial assessed a novel, experience-based website containing personal accounts of quitting smoking as a cessation intervention, and a comparator website providing factual information. Feasibility measures including recruitment, and usage of the interventions were recorded, and the following participant-reported outcomes were also measured: Smoking Abstinence Self-Efficacy Questionnaire, the single-item Motivation to Stop Scale, self-reported abstinence, quit attempts and health status outcomes. Eligible smokers from two English regions were entered into the trial and given access to their allocated website for two weeks. Results Eighty-seven smokers were randomised, 65 completed follow-up (75 %. Median usage was 15 min for the intervention, and 5 min for the comparator (range 0.5–213 min. Median logins for both sites was 2 (range 1–20. All participant-reported outcomes were similar between groups. Conclusions It was technically feasible to deliver a novel intervention harnessing the online sharing of personal experiences as a tool for smoking cessation, but recruitment was slow and actual use was relatively low, with attrition from the trial. Future work needs to maximize engagement and to understand how best to assess the value of such interventions in everyday use, rather than as an isolated ‘dose of information’. Trial registration ISRCTN29549695 DOI 10.1186/ISRCTN29549695 . Registered 17/05/2013.
Byakika-Kibwika, Pauline; Achan, Jane; Lamorde, Mohammed; Karera-Gonahasa, Carine; Kiragga, Agnes N; Mayanja-Kizza, Harriet; Kiwanuka, Noah; Nsobya, Sam; Talisuna, Ambrose O; Merry, Concepta
Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda. We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1-2) vs 3 (2-3), P malaria symptoms. In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed. The study was registered with the Pan African Clinical Trial Registry ( PACTR201110000321348 ).
Paterniti, Debora A.; Chen, Moon S.; Chiechi, Christine; Beckett, Laurel A.; Horan, Nora; Turrell, Corinne; Smith, Ligaya; Morain, Claudia; Montell, Lisa; Gonzalez, Jose Luis; Davis, Sharon; Lara, Primo N.
Cancer clinical trials have been based on low accrual rates. Barriers to recruitment of minority populations affect the generalizability and impact of trial findings for those populations. The authors undertook a mixed-methods approach to understanding levels of awareness and experiences with cancer clinical trials. A survey was administered to new cancer patients and their caretakers (family, close friends, or other social support) at outpatient oncology clinics. Field observations of the trial accrual process also were conducted by employing the grounded theory approach in qualitative methods. Comparison of survey results for Asian-American respondents and non-Asian respondents indicated that Asians were less likely to have heard the term “clinical trial” and were more likely to define a clinical trial as “an experiment” or “a test procedure in a clinic” than non-Asians. Asians were more likely to have employer-based insurance and to report understanding issues related to cost reimbursement. Asians were less likely to have been involved in or to know someone in a trial and reported less willingness than white respondents to consider trial participation. Qualitative observations suggested that Asians who presented for a potential trial were interested in the availability of a novel cancer therapy but were not eligible for available trials. Multiple strategies will be necessary to enhance awareness of and experience with accrual to cancer clinical trials for Asians, including richer understanding and increased involvement of Asians in cancer clinical trials and greater attention to the location and diversity of the Asian population in structuring study centers and evaluating trial results. PMID:16247795
Weimand, B M; Israel, P; Ewertzon, M
International research shows that relatives of people with mental illness are rarely involved by mental health services. Assertive Community Treatment (ACT) has been recently implemented in Norway. The experience of relatives of ACT users is largely unknown. The aim of this study was to explore relatives' experience with ACT-teams in Norway. Data were collected using the family involvement and alienation questionnaire, consisting of experiences of approach, and alienation from the provision of professional care. 38 Relatives participated in this study. A majority experienced a positive approach (openness, confirmation, and cooperation) from the ACT teams, which also was considered better compared to previous services. They considered openness and cooperation as essential aspects from the professionals. Almost half did not feel alienated (powerlessness and social isolation). Higher level of being approached positively was significantly associated with lower level of feeling alienated. The knowledge of what constituted relatives' positive experiences with the ACT teams should be transferred into practice regarding how to form a positive alliance with relatives.
Bogossian, Fiona E; Cooper, Simon J; Cant, Robyn; Porter, Joanne; Forbes, Helen
High-fidelity simulation pedagogy is of increasing importance in health professional education; however, face-to-face simulation programs are resource intensive and impractical to implement across large numbers of students. To investigate undergraduate nursing students' theoretical and applied learning in response to the e-simulation program-FIRST2ACT WEBTM, and explore predictors of virtual clinical performance. Multi-center trial of FIRST2ACT WEBTM accessible to students in five Australian universities and colleges, across 8 campuses. A population of 489 final-year nursing students in programs of study leading to license to practice. Participants proceeded through three phases: (i) pre-simulation-briefing and assessment of clinical knowledge and experience; (ii) e-simulation-three interactive e-simulation clinical scenarios which included video recordings of patients with deteriorating conditions, interactive clinical tasks, pop up responses to tasks, and timed performance; and (iii) post-simulation feedback and evaluation. Descriptive statistics were followed by bivariate analysis to detect any associations, which were further tested using standard regression analysis. Of 409 students who commenced the program (83% response rate), 367 undergraduate nursing students completed the web-based program in its entirety, yielding a completion rate of 89.7%; 38.1% of students achieved passing clinical performance across three scenarios, and the proportion achieving passing clinical knowledge increased from 78.15% pre-simulation to 91.6% post-simulation. Knowledge was the main independent predictor of clinical performance in responding to a virtual deteriorating patient R(2)=0.090, F(7, 352)=4.962, plearning. The web-based e-simulation program FIRST2ACTTM effectively enhanced knowledge, virtual clinical performance, and self-assessed knowledge, skills, confidence, and competence in final-year nursing students. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available Abstract Background The long acting β2-agonists, salmeterol and formoterol, have been recommended, by some, as first line treatment of stable chronic obstructive pulmonary disease (COPD. We reviewed evidence of efficacy and safety when compared with placebo or anticholinergic agents in patients with poorly reversible COPD. Methods After searching MEDLINE, EMBASE, HealthSTAR, BIOSIS Previews, PASCAL, ToxFile, SciSearch, the Cochrane Library, and PubMed, as well as Web sites, selected journals, reference lists, and contacting drug manufacturers, two reviewers independently screened reports of randomised controlled trials of parallel or crossover design lasting four weeks or longer and including patients with a forced expiratory volume in one second (FEV1 ≤ 75% of predicted, a ratio of FEV1 to forced vital capacity (FVC ≤ 88% of predicted, and Results Twelve trials satisfied our inclusion criteria; eight were high quality (Jadad score >2 and four were low quality (≤ 2. The adequacy of allocation concealment was unclear in all of them. We did not perform a meta-analysis due to differences in trial design and how outcomes were reported. Two trials comparing salmeterol with ipratropium did not detect differences; one trial comparing formoterol and ipratropium described greater improvement with formoterol in morning PEFR (15.3 versus 7.1 l/min, p = 0.040. Of twelve trials comparing long acting β2 agonists with placebo, six reported no improvement in exercise capacity, eleven reported improvements in FEV1 lung function (one reported no improvement, six reported less rescue inhaler usage (one reported no difference and five reported improved dyspnea scores (two reported no improvement. Differences in quality of life were detected in one salmeterol trial ; however, two salmeterol, and one formoterol trial reported no differences. Adverse effects of interest were not reported. Conclusion In terms of clinical outcomes and safety, we could not find
Aquino, Karl; McFerran, Brent; Laven, Marjorie
Four studies using survey and experimental designs examined whether people whose moral identity is highly self-defining are more susceptible to experiencing a state of moral elevation after being exposed to acts of uncommon moral goodness. Moral elevation consists of a suite of responses that motivate prosocial action tendencies. Study 1 showed that people higher (vs. lower) in moral identity centrality reported experiencing more intense elevating emotions, had more positive views of humanity, and were more desirous of becoming a better person after reading about an act of uncommon goodness than about a merely positive situation or an act of common benevolence. Study 2 showed that those high in moral identity centrality were more likely to recall acts of moral goodness and experience moral elevation in response to such events more strongly. These experiences were positively related to self-reported prosocial behavior. Study 3 showed a direct effect on behavior using manipulated, rather than measured, moral identity centrality. Study 4 replicated the effect of moral identity on the states of elevation as well as on self-reported physical sensations and showed that the elevation mediates the relationship between moral identity, witnessing uncommon goodness, and prosocial behavior.
Powell, John; Newhouse, Nikki; Martin, Angela; Jawad, Sena; Yu, Ly-Mee; Davoudianfar, Mina; Locock, Louise; Ziebland, Sue
The internet is frequently used to share experiences of health and illness, but this phenomenon has not been harnessed as an intervention to achieve health behaviour change. The aim of this study was to determine the feasibility of a randomised trial assessing the effects of a novel, experience-based website as a smoking cessation intervention. The secondary aim was to measure the potential impact on smoking behaviour of both the intervention and a comparator website. A feasibility randomised controlled single-blind trial assessed a novel, experience-based website containing personal accounts of quitting smoking as a cessation intervention, and a comparator website providing factual information. Feasibility measures including recruitment, and usage of the interventions were recorded, and the following participant-reported outcomes were also measured: Smoking Abstinence Self-Efficacy Questionnaire, the single-item Motivation to Stop Scale, self-reported abstinence, quit attempts and health status outcomes. Eligible smokers from two English regions were entered into the trial and given access to their allocated website for two weeks. Eighty-seven smokers were randomised, 65 completed follow-up (75 %). Median usage was 15 min for the intervention, and 5 min for the comparator (range 0.5-213 min). Median logins for both sites was 2 (range 1-20). All participant-reported outcomes were similar between groups. It was technically feasible to deliver a novel intervention harnessing the online sharing of personal experiences as a tool for smoking cessation, but recruitment was slow and actual use was relatively low, with attrition from the trial. Future work needs to maximize engagement and to understand how best to assess the value of such interventions in everyday use, rather than as an isolated 'dose of information'. ISRCTN29549695 DOI 10.1186/ISRCTN29549695 . Registered 17/05/2013.
Harvey, Merryl; Nongena, Phumza; Edwards, David; Redshaw, Maggie
Studies exploring parents' trial experiences generally relate to their understanding of the consent process and the development of researcher strategies to facilitate recruitment and retention. The aim was to better understand parents' experience of being part of a trial at the time and their perceptions of trial participation in retrospect. Data were collected in a number of ways: from recorded discussions between parents and clinicians about the MRI or ultrasound, in open-text responses to questionnaires and in qualitative interviews at 1 and 2 years after participation. Thematic analysis was undertaken using NVivo10. Key themes identified were 'deciding to take part', with subthemes associated with 'benefitting self', 'benefitting others' and 'being prepared'; 'the randomisation process' with subthemes relating to 'acceptance' and 'understanding' and 'actual engagement' with subthemes of 'practicalities' and 'care from responsive staff'. Parents' perspectives on the trial and the processes and information received reflect their understanding and experience of the trial and the value of parent-friendly information-giving about participation, randomisation and follow-up. The practical and logistical points raised confirm the key issues and parents' need for sensitive care and support in the course of a trial. Looking back, almost all parents were positive about their experience and felt that the family had benefitted from participation in the trial and follow-up studies, even when the developmental outcomes were poor. ClinicalTrials.gov, ID: NCT01049594. https://clinicaltrials.gov/ct2/show/NCT01049594 . Registered on 13 January 2010. EudraCT: EudraCT: 2009-011602-42. https://www.clinicaltrialsregister.eu/ .
Sawyer, Alexandra; Chhoa, Celine; Ayers, Susan; Pushpa-Rajah, Angela; Duley, Lelia
The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. In addition to standard written consent, an oral assent pathway was developed for use when birth was imminent. The aim of this study was to explore women's views and experiences of two alternative consent pathways to participate in the Cord Pilot Trial. We conducted a qualitative study using semi-structured interviews. A total of 179 participants in the Cord Pilot Trial were sent a postal invitation to take part in interviews. Women who agreed were interviewed in person or by telephone to explore their experiences of two consent pathways for a preterm intrapartum trial. Data were analysed using inductive systematic thematic analysis. Twenty-three women who gave either written consent (n = 18) or oral assent followed by written consent (n = 5) to participate in the trial were interviewed. Five themes were identified: (1) understanding of the implications of randomisation, (2) importance of staff offering participation, (3) information about the trial and time to consider participation, (4) trial secondary in women's minds and (5) reasons for agreeing to take part in the trial. Experiences were similar for the two consent pathways. Women recruited by the oral assent pathway reported being given less information about the trial but felt it was sufficient to make a decision regarding participation. There were gaps in women's understanding of the trial and intervention, regardless of the consent pathway. Overall, women were positive about their experiences of being invited to participate in the trial. The oral assent pathway seems an acceptable option for women if the intervention is low-risk and time is limited. ISRCTN Registry, ISRCTN21456601 . Registered on 28 February 2013.
The UK Equal Pay Act of 1970 resulted in a large rise in the relative earnings of women in the early 1970s. As this change (unlike most wage changes) was largely exogenous to employers, one can think of this episode as an experiment for testing different theories of the labour market. Hence, study of the effects of the Equal Pay Act should be given considerable weight and is likely to have wider implications about the operation of labour markets. Most models of the labour market used by econo...
In response to the Home Office recommendations contained in Speaking Up for Justice (1998) the Youth Justice and Criminal Evidence Act (YJCEA) 1999 introduced a new regime for the conduct of sexual offence trials. Section 41 of the Act, which came into force on 4 December 2000, brings about dramatic changes to the rules on the admissibility of evidence of complainants' sexual behaviour, severely restricting the discretion of trial judges to introduce such evidence or to allow questioning concerning it. This represents a radical new departure that will fundamentally affect an accused's position at trial. Responses to section 41 have predictably been divided given the extremely sensitive nature of this area of the law of evidence and the complex set of social and political issues which are at stake. Many have greeted it as a long overdue reform of a system premised upon outmoded and sexist beliefs concerning women's sexual behaviour which has routinely functioned to admit prejudicial and irrelevant evidence. Others, predominantly within the legal profession, have expressed serious concerns over whether the new law is workable and the extent to which, by potentially excluding critically relevant evidence, it may infringe upon a defendant's right to a fair trial. The quality of the legislation is soon to be tested. On 26 and 27 March 2001 the House of Lords heard an interlocutory appeal in the case of R v. A and were asked to decide if the new provisions, by excluding previous sexual history evidence between the complainant and the defendant, contravened Article 6 of the European Convention of Human Rights. Their Lordships are, at the time of writing, yet to give judgment and the fate of the defendant in question, and several others whose trials have been postponed pending their decision, hangs in the balance. This article seeks to show that the new Act, despite being well-intentioned, does not adopt a coherent or sustainable approach to the relevance of previous
Joly, Joanna M; Desai, Akshay S
Compared to enalapril, use of angiotensin-receptor blocker and neprilysin inhibitor sacubitril/valsartan to treat patients with heart failure and reduced ejection fraction (HFrEF) is associated with substantial reductions in both cardiovascular mortality and heart failure progression. The purpose of this review is to discuss the real-world experience of sacubitril/valsartan. In the years following the publication of the landmark PARADIGM-HF trial in 2014 and its subsequent FDA approval, a growing evidence base supports the safety and efficacy of sacubitril/valsartan in a broad spectrum of patients with HFrEF. Updated clinical practice guidelines have embraced the use of sacubitril/valsartan in preference to ACE inhibitors or ARBs in selected patients. In this review, we highlight the clinical trials that led to these key updates to clinical guidelines, offer practical strategies for patient selection and utilization in clinical practice, and identify important areas of uncertainty that require future research.
Full Text Available Abstract One reason for doing randomised controlled trials (RCTs is that experiments can be convincing. Early epidemiological experimenters, such as Jenner and the smallpox vaccine and Snow and his famous Broad Street pump handle, already knew the answer they were demonstrating; they used the experiments as knowledge translation devices to convince others. More sophisticated modern experiments include cluster randomised controlled trials (CRCTs for experiments in the public health setting. The knowledge translation value remains: RCTs and CRCTs can potentially stimulate changes of practice among stakeholders. Capitalising on the knowledge translation value of RCTs requires more than the standard reporting of trials. Those who are convinced by a trial and want to act, need to know how the trial relates to their own context, what contributed to success, and what might make it even more effective. Implementation research unpacks the back-story, examining how and why an intervention worked. The Camino Verde trial of community mobilisation for control of dengue reported a significant impact on entomological indices of the Aedes aegypti vector, and on serological dengue virus infection and self-reported dengue cases. This important study should lead to studies of similar interventions in other contexts, and ultimately to changes in dengue control practices. This supplement is the back-story of the trial, providing information to help researchers and planners to make use of the trial findings. Background articles include the full protocol, a systematic review of CRCTs of approaches for Aedes aegypti control, epidemiological and entomological findings from the baseline survey, and how baseline findings were used to set up the intervention. Secondary analyses of the entomological findings examine associations with the use of the larvicide temephos, and the impact of the intervention in different conditions of water supply and seasons. Other articles
Murray-Davis, Beth; Marion, Anya; Malott, Anne; Reitsma, Angela; Hutton, Eileen K
The international, multicenter External Cephalic Version 2 (ECV2) Trial compared early external cephalic version at 34(0/7) to 35(6/7) weeks with that at greater than 37 weeks. A total of 1,543 women were randomized from 68 centers in 21 countries. The goal of this component of the trial was to understand women's views about participation in a research trial and timing of external cephalic version. A postpartum questionnaire was completed containing a 5-point Likert scale examining contact and availability of staff, choice of timing of external cephalic version, preference of randomization, convenience of participating, and overall satisfaction. Participants also completed two open-ended questions related to timing of external cephalic version and satisfaction with the trial. Descriptive statistics and content analysis were used to analyze data. A total of 1,458 women completed the questionnaire, of whom 86 percent said "yes"-they would participate in the trial again. Themes influencing decisions about participating were perceptions of the external cephalic version experience, preferred mode of delivery, preferred timing of external cephalic version, and perceptions of the effectiveness of external cephalic version and of the trial environment. Many participants preferred the early timing of the procedure offered through the trial because of perceived advantages of a smaller baby being easier to turn and the opportunity for repeat procedures. Women were positive about their participation in the trial. Early external cephalic version was preferred over the traditional timing as it was perceived to afford both physiologic and practical advantages. © 2012, Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc.
Bill-Axelson, Anna; Christensson, Anna; Carlsson, Marianne; Norlén, Bo Johan; Holmberg, Lars
Recruitment of both patients and clinicians to randomized trials is difficult. Low participation carries the risk of terminating studies early and making them invalid owing to insufficient statistical power. This study investigated patients' and clinicians' experiences of randomization with the aim of facilitating trial participation in the future. This was a qualitative study using content analysis. Patients offered to participate in a randomized trial and randomizing clinicians were interviewed. Five participants, four non-participants and five randomizing clinicians were interviewed, 2-8 years from randomization. Clinicians used strategies in interaction with the patients to facilitate decision making. Patients' attitudes differed and experiences of relatives or friends were often stated as reasons for treatment preferences. Patients described that letting chance decide treatment was a difficult barrier to overcome for randomization. The clinicians used a number of different strategies perceived to make randomization more acceptable to their patients. The clinicians' own motivation for randomizing patients for trials depended on the medical relevance of the study question and the clinicians' major obstacle was to maintain equipoise over time. Regular meetings with the study group helped to maintain equipoise and motivation. To establish a good platform for randomization the clinician needs to know about the patient's treatment preferences and the patient's attitude concerning the role of the clinician to facilitate decision making. The strategies used by the clinicians were perceived as helpful and could be tested in an intervention study.
Full Text Available Background: Opportunities to use data and information to address challenges in international agricultural research and development are expanding rapidly. The use of agricultural trial and evaluation data has enormous potential to improve crops and management practices. However, for a number of reasons, this potential has yet to be realized. This paper reports on the experience of the AgTrials initiative, an effort to build an online database of agricultural trials applying principles of interoperability and open access. Methods: Our analysis evaluates what worked and what did not work in the development of the AgTrials information resource. We analyzed data on our users and their interaction with the platform. We also surveyed our users to gauge their perceptions of the utility of the online database. Results: The study revealed barriers to participation and impediments to interaction, opportunities for improving agricultural knowledge management and a large potential for the use of trial and evaluation data. Conclusions: Technical and logistical mechanisms for developing interoperable online databases are well advanced. More effort will be needed to advance organizational and institutional work for these types of databases to realize their potential.
Full Text Available Background: Opportunities to use data and information to address challenges in international agricultural research and development are expanding rapidly. The use of agricultural trial and evaluation data has enormous potential to improve crops and management practices. However, for a number of reasons, this potential has yet to be realized. This paper reports on the experience of the AgTrials initiative, an effort to build an online database of agricultural trials applying principles of interoperability and open access. Methods: Our analysis evaluates what worked and what did not work in the development of the AgTrials information resource. We analyzed data on our users and their interaction with the platform. We also surveyed our users to gauge their perceptions of the utility of the online database. Results: The study revealed barriers to participation and impediments to interaction, opportunities for improving agricultural knowledge management and a large potential for the use of trial and evaluation data. Conclusions: Technical and logistical mechanisms for developing interoperable online databases are well advanced. More effort will be needed to advance organizational and institutional work for these types of databases to realize their potential.
Fried, Linda P.; Carlson, Michelle C.; McGill, Sylvia; Seeman, Teresa; Xue, Qian-Li; Frick, Kevin; Tan, Erwin; Tanner, Elizabeth K.; Barron, Jeremy; Frangakis, Constantine; Piferi, Rachel; Martinez, Iveris; Gruenewald, Tara; Martin, Barbara K.; Berry-Vaughn, Laprisha; Stewart, John; Dickersin, Kay; Willging, Paul R.; Rebok, George W.
Background As the population ages, older adults are seeking meaningful, and impactful, post-retirement roles. As a society, improving the health of people throughout longer lives is a major public health goal. This paper presents the design and rationale for an effectiveness trial of Experience Corps™, an intervention created to address both these needs. This trial evaluates (1) whether senior volunteer roles within Experience Corps™ beneficially impact children's academic achievement and classroom behavior in public elementary schools and (2) impact on the health of volunteers. Methods Dual evaluations of (1) an intention-to-treat trial randomizing eligible adults 60 and older to volunteer service in Experience Corps™, or to a control arm of usual volunteering opportunities, and (2) a comparison of eligible public elementary schools receiving Experience Corps™ to matched, eligible control schools in a 1:1 control:intervention school ratio. Outcomes For older adults, the primary outcome is decreased disability in mobility and Instrumental Activities of Daily Living (IADL). Secondary outcomes are decreased frailty, falls, and memory loss; slowed loss of strength, balance, walking speed, cortical plasticity, and executive function; objective performance of IADLs; and increased social and psychological engagement. For children, primary outcomes are improved reading achievement and classroom behavior in Kindergarten through the 3rd grade; secondary outcomes are improvements in school climate, teacher morale and retention, and teacher perceptions of older adults. Summary This trial incorporates principles and practices of community-based participatory research and evaluates the dual benefit of a single intervention, versus usual opportunities, for two generations: older adults and children. PMID:23680986
Full Text Available Abstract Whilst some populations have recently experienced dramatic declines in malaria, the majority of those most at risk of Plasmodium falciparum malaria still lack access to effective treatment with artemisinin combination therapy (ACT and others are already facing parasites resistant to artemisinins. In this context, there is a crucial need to improve both access to and targeting of ACT through greater availability of good quality ACT and parasitological diagnosis. This is an issue of increasing urgency notably in the private commercial sector, which, in many countries, plays an important role in the provision of malaria treatment. The Affordable Medicines Facility for malaria (AMFm is a recent initiative that aims to increase the provision of affordable ACT in public, private and NGO sectors through a manufacturer-level subsidy. However, to date, there is little documented experience in the programmatic implementation of subsidized ACT in the private sector. Cambodia is in the unique position of having more than 10 years of experience not only in implementing subsidized ACT, but also rapid diagnostic tests (RDT as part of a nationwide social marketing programme. The programme includes behaviour change communication and the training of private providers as well as the sale and distribution of Malarine, the recommended ACT, and Malacheck, the RDT. This paper describes and evaluates this experience by drawing on the results of household and provider surveys conducted since the start of the programme. The available evidence suggests that providers' and consumers' awareness of Malarine increased rapidly, but that of Malacheck much less so. In addition, improvements in ACT and RDT availability and uptake were relatively slow, particularly in more remote areas. The lack of standardization in the survey methods and the gaps in the data highlight the importance of establishing a clear system for monitoring and evaluation for similar initiatives
Grigg, M J; William, T; Dhanaraj, P; Menon, J; Barber, B E; von Seidlein, L; Rajahram, G; Price, R N; Anstey, N M; Yeo, T W
Malaria due to Plasmodium knowlesi is reported throughout South-East Asia, and is the commonest cause of it in Malaysia. P. knowlesi replicates every 24 h and can cause severe disease and death. Current 2010 WHO Malaria Treatment Guidelines have no recommendations for the optimal treatment of non-severe knowlesi malaria. Artemisinin-combination therapies (ACT) and chloroquine have each been successfully used to treat knowlesi malaria; however, the rapidity of parasite clearance has not been prospectively compared. Malaysia's national policy for malaria pre-elimination involves mandatory hospital admission for confirmed malaria cases with discharge only after two negative blood films; use of a more rapidly acting antimalarial agent would have health cost benefits. P. knowlesi is commonly microscopically misreported as P. malariae, P. falciparum or P. vivax, with a high proportion of the latter two species being chloroquine-resistant in Malaysia. A unified ACT-treatment protocol would provide effective blood stage malaria treatment for all Plasmodium species. ACT KNOW, the first randomised controlled trial ever performed in knowlesi malaria, is a two-arm open-label trial with enrolments over a 2-year period at three district sites in Sabah, powered to show a difference in proportion of patients negative for malaria by microscopy at 24 h between treatment arms (clinicaltrials.gov #NCT01708876). Enrolments started in December 2012, with completion expected by September 2014. A total sample size of 228 is required to give 90% power (α 0.05) to determine the primary end point using intention-to-treat analysis. Secondary end points include parasite clearance time, rates of recurrent infection/treatment failure to day 42, gametocyte carriage throughout follow-up and rates of anaemia at day 28, as determined by survival analysis. This study has been approved by relevant institutional ethics committees in Malaysia and Australia. Results will be disseminated to inform
Srivastava, Prachi; Noronha, Claire
We examine relative household costs and experiences of accessing private and government schooling under India's "Right of Children to Free and Compulsory Education Act, 2009" in the early implementation phase. The Act deems that no child should incur any fee, charges, or expenses in accessing schooling. Private schools are mandated to…
Hedberg, Katrina; New, Craig
Twenty years ago, Oregon voters approved the Death With Dignity Act, making Oregon the first state in the United States to allow physicians to prescribe medications to be self-administered by terminally ill patients to hasten their death. This report summarizes the experience in Oregon, including the numbers and types of participating patients and providers. These data should inform the ongoing policy debate as additional jurisdictions consider such legislation.
Full Text Available ... studies. View funding information for clinical trials optimization . Building 31 31 Center Drive Bethesda, MD 20892 Learn ... and Usage No FEAR Act Grants and Funding Building 31 31 Center Drive Bethesda, MD 20892 Learn ...
McBain, Bonnie; Drew, Antony; James, Carole; Phelan, Liam; Harris, Keith M; Archer, Jennifer
Purpose: The purpose of this paper is to evaluate the experiences of tertiary students learning oral presentation skills in a range of online and blended learning contexts across diverse disciplines. Design/methodology/approach: The research was designed as a "federation" of trials of diverse online oral communications assessment tasks…
Full Text Available ... and organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense ... FOIA) Accessibility Copyright and Usage No FEAR Act Grants and Funding Building 31 31 Center Drive Bethesda, ...
In a self-critical inquiry into my own recent work of co-curating and the experience of seeing my video work being curated by others, this article examines acts of framing as performative acts that seek to transform visitors' preconceptions. This affective effect is pursued by means of immersion,
Cortellini, Mauro; Berrino, Franco; Pasanisi, Patrizia
Among randomized controlled trials (RCTs), trials for primary prevention require large samples and long follow-up to obtain a high-quality outcome; therefore the recruitment process and the drop-out rates largely dictate the adequacy of the results. We are conducting a Phase III trial on persons with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]). Here, we briefly analyze and discuss the reasons which may lead to participants dropping out from trials. In our experience, participants may back out of a trial for different reasons. Drug-induced side effects are certainly the most compelling reason. But what are the other reasons, relating to the participants' perception of the progress of the trial which led them to withdraw after randomization? What about the time-dependent drop-out rate in primary prevention trials? The primary outcome of this analysis is the point of drop-out from trial, defined as the time from the randomization date to the withdrawal date. Survival functions were non-parametrically estimated using the product-limit estimator. The curves were statistically compared using the log-rank test ( P =0.64, not significant). Researchers involved in primary prevention RCTs seem to have to deal with the paradox of the proverbial "short blanket syndrome". Recruiting only highly motivated candidates might be useful for the smooth progress of the trial but it may lead to a very low enrollment rate. On the other hand, what about enrolling all the eligible subjects without considering their motivation? This might boost the enrollment rate, but it can lead to biased results on account of large proportions of drop-outs. Our experience suggests that participants do not change their mind depending on the allocation group (intervention or control). There is no single
Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.
Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID
Alexander W Dromerick
Full Text Available Introduction: 795,000 Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 hours of upper extremity therapy either immediately upon rehab admission, 2-3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test at one year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial.
Full Text Available Abstract Background Evaluating complex interventions in health services faces various difficulties, such as making practice changes and costs. Ways to increase research capacity and decrease costs include making research an integral part of health services and using routine data to judge outcomes. The purpose of this article is to report the feasibility of a pilot trial relying solely on routinely collected register data and being based on ordinary health services. Methods The example intervention was education to public health nurses (PHN (childbirth classes to reduce caesarean section rates via pre-delivery considerations of pregnant women. 20 maternity health centers (MHC were paired and of each 10 pairs, one MHC was randomly allocated to an intervention group and the other to a control; 8 pairs with successful intervention were used in the analyses (1601 mothers. The women visiting to the study maternity centers were identified from the Customer Register of Helsinki City. A list of the study women was made using the mother's personal identification number, visit date, the maternity center code, birth date and gestation length. The mode of delivery and health outcomes were retrieved from the Finnish Medical Birth Register (MBR. Process data of the intervention are based on observations, written feedback and questionnaires from PHNs, and project correspondence. Results It took almost two years to establish how to obtain permissions and to actually obtain it for the trial. Obtaining permissions for the customer and outcome data and register linkages was unproblematic and the cluster randomization provided comparable groups. The intervention did not succeed well. Had the main aim of the trial been to cause a change in PHNs behavior, we would have very likely intensified the intervention during the trial. Conclusion Our experiences encourage the use of trials that obtain their outcomes from registers. Changing the behavior of ordinary health
Toledo, Lauren; McLellan-Lemal, Eleanor; Henderson, Faith L; Kebaabetswe, Poloko M
Recent clinical trials have shown that a daily dose of oral TDF/FTC pre-exposure prophylaxis (PrEP) is effective in reducing human immunodeficiency (HIV) risk. Understanding trial participants' perspectives about retention and PrEP adherence is critical to inform future PrEP trials and the scale-up and implementation of PrEP programs. We analyzed 53 in-depth interviews conducted in April 2010 with participants in the TDF2 study, a Phase 3, randomized, double-blind, placebo-controlled clinical trial of daily oral TDF/FTC with heterosexual men and women in Francistown and Gaborone, Botswana. We examined participants' knowledge, attitudes, and experiences of the trial, identified facilitators and barriers to enrollment and retention, and compared participant responses by study site, sex, and study drug adherence. Our findings point to several factors to consider for participant retention and adherence in PrEP trials and programs, including conducting pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of non-adherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants.
Symonds, R P; Lord, K; Mitchell, A J; Raghavan, D
Throughout the world there are problems recruiting ethnic minority patients into cancer clinical trials. A major barrier to trial entry may be distrust of research and the medical system. This may be compounded by the regulatory framework governing research with an emphasis on written consent, closed questions and consent documentation, as well as fiscal issues. The Leicester UK experience is that trial accrual is better if British South Asian patients are approached by a senior doctor rather than someone of perceived lesser hierarchical status and a greater partnership between the hospital and General Practitioner may increase trial participation of this particular ethnic minority. In Los Angeles, USA, trial recruitment was improved by a greater utilisation of Hispanic staff and a Spanish language-based education programme. Involvement of community leaders is essential. While adhering to national, legal and ethnical standards, information sheets and consent, it helps if forms can be tailored towards the local ethnic minority population. Written translations are often of limited value in the recruitment of patients with no or limited knowledge of English. In some cultural settings, tape-recorded verbal consent (following approval presentations) may be an acceptable substitute for written consent, and appropriate legislative changes should be considered to facilitate this option. Approaches should be tailored to specific minority populations, taking consideration of their unique characteristics and with input from their community leadership.
Full Text Available Mauro Cortellini, Franco Berrino, Patrizia Pasanisi Department of Preventive & Predictive Medicine, Foundation IRCCS National Cancer Institute of Milan, Milan, Italy Abstract: Among randomized controlled trials (RCTs, trials for primary prevention require large samples and long follow-up to obtain a high-quality outcome; therefore the recruitment process and the drop-out rates largely dictate the adequacy of the results. We are conducting a Phase III trial on persons with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]. Here, we briefly analyze and discuss the reasons which may lead to participants dropping out from trials. In our experience, participants may back out of a trial for different reasons. Drug-induced side effects are certainly the most compelling reason. But what are the other reasons, relating to the participants’ perception of the progress of the trial which led them to withdraw after randomization? What about the time-dependent drop-out rate in primary prevention trials? The primary outcome of this analysis is the point of drop-out from trial, defined as the time from the randomization date to the withdrawal date. Survival functions were non-parametrically estimated using the product-limit estimator. The curves were statistically compared using the log-rank test (P=0.64, not significant. Researchers involved in primary prevention RCTs seem to have to deal with the paradox of the proverbial “short blanket syndrome”. Recruiting only highly motivated candidates might be useful for the smooth progress of the trial but it may lead to a very low enrollment rate. On the other hand, what about enrolling all the eligible subjects without considering their motivation? This might boost the enrollment rate, but it can lead to biased
MacNeill, Virginia; Foley, Marian; Quirk, Alan; McCambridge, Jim
The sequence of events in a behaviour change trial involves interactions between research participants and the trial process. Taking part in such a study has the potential to influence the behaviour of the participant, and if it does, this can engender bias in trial outcomes. Since participants' experience has received scant attention, the aim of this study is thus to generate hypotheses about which aspects of the conduct of behaviour change trials might matter most to participants, and thus have potential to alter subsequent behaviours and bias trial outcomes Twenty participants were opportunistically screened for a health compromising behaviour (unhealthy diet, lack of exercise, smoking or alcohol consumption) and recruited if eligible. Semi structured face to face interviews were conducted, after going through the usual processes involved in trial recruitment, baseline assessment and randomisation. Participants were given information on the contents of an intervention or control condition in a behaviour change trial, which was not actually implemented. Three months later they returned to reflect on these experiences and whether they had any effect on their behaviour during the intervening period. Data from the latter interview were analysed thematically using a modified grounded theory approach. The early processes of trial participation raised awareness of unhealthy behaviours, although most reported having had only fleeting intentions to change their behaviour as a result of taking part in this study, in the absence of interventions. However, careful examination of the accounts revealed evidence of subtle research participation effects, which varied according to the health behaviour, and its perceived social acceptability. Participants' relationships with the research study were viewed as somewhat important in stimulating thinking about whether and how to make lifestyle changes. These participants described no dramatic impacts attributable to taking part in
Full Text Available Abstract Background South Africa, with its scientific capacity, good infrastructure and high HIV incidence rates, is ideally positioned to conduct large-scale HIV prevention trials. The HIV Prevention Research Unit of the South African Medical Research Council conducted four phase III and one phase IIb trials of women-initiated HIV prevention options in KwaZulu-Natal between 2003 and 2009. A total of 7046 women participated, with HIV prevalence between 25% and 45% and HIV incidence ranging from 4.5-9.1% per year. Unfortunately none of the interventions tested had any impact on reducing the risk of HIV acquisition; however, extremely valuable experience was gained, lessons learned and capacity built, while the communities gained associated benefits. Experience Our experience in conducting these trials ranged from setting up community partnerships to developing clinical research sites and dissemination of trial results. Community engagement included setting up community-based research sites with approval from both political and traditional leaders, and developing community advisory groups to assist with the research process. Community-wide education on HIV/sexually transmitted infection prevention, treatment and care was provided to over 90 000 individuals. Myths and misconceptions were addressed through methods such as anonymous suggestion boxes in clinic waiting areas and intensive education and counselling. Attempts were made to involve male partners to foster support and facilitate recruitment of women. Peer educator programmes were initiated to provide ongoing education and also to facilitate recruitment of women to the trials. Recruitment strategies such as door-to-door recruitment and community group meetings were initiated. Over 90% of women enrolled were retained. Community benefits from the trial included education on HIV prevention, treatment and care and provision of ancillary care (such as Pap smears, reproductive health care and
Kongsted, Alice; Montvilas, Erisela Qerama; Kasch, Helge
practitioners within 10 days after a whiplash injury and randomized to: 1) immobilization of the cervical spine in a rigid collar followed by active mobilization, 2) advice to "act-as-usual," or 3) an active mobilization program (Mechanical Diagnosis and Therapy). Follow-up was carried out after 3, 6, and 12......-extension trauma to the cervical spine. It is unclear whether this, in some cases disabling, condition can be prevented by early intervention. Active interventions have been recommended but have not been compared with information only. Methods. Participants were recruited from emergency units and general......Study Design. Randomized, parallel-group trial. Objective. To compare the effect of 3 early intervention strategies following whiplash injury. Summary of Background Data. Long-lasting pain and disability, known as chronic whiplash-associated disorder (WAD), may develop after a forced flexion...
Kongsted, Alice; Montvilas, Erisela Qerama; Kasch, Helge
Study Design. Randomized, parallel-group trial. Objective. To compare the effect of 3 early intervention strategies following whiplash injury. Summary of Background Data. Long-lasting pain and disability, known as chronic whiplash-associated disorder (WAD), may develop after a forced flexion......-extension trauma to the cervical spine. It is unclear whether this, in some cases disabling, condition can be prevented by early intervention. Active interventions have been recommended but have not been compared with information only. Methods. Participants were recruited from emergency units and general...... practitioners within 10 days after a whiplash injury and randomized to: 1) immobilization of the cervical spine in a rigid collar followed by active mobilization, 2) advice to "act-as-usual," or 3) an active mobilization program (Mechanical Diagnosis and Therapy). Follow-up was carried out after 3, 6, and 12...
The case described in this paper involves the interpretation of language contained in the Texas Clean Air Act Texas Health and Safety Code Ann. Sections 382.001-382.141. The State of Texas, on behalf of the Texas Air Control Board, brought suit in the District Court of Erath County, Texas against the F/R Cattle Company, Inc., alleging that, because of odors emanating from the company's cattle feeding facility, the company was violating the Clean Air Act. The Board is granted the power and duty to administer the Clean Air Act and is directed to accomplish the purposes of the Act through the control of air contaminants by all practical and economically feasible methods. Described here is the evidence presented at and proceedings of the trial
Breccia, Massimo; Stagno, Fabio; Luciano, Luigiana; Abruzzese, Elisabetta; Annunziata, Mario; D'Adda, Mariella; Maggi, Alessandro; Sgherza, Nicola; Russo-Rossi, Antonella; Pregno, Patrizia; Castagnetti, Fausto; Iurlo, Alessandra; Latagliata, Roberto; Cedrone, Michele; Di Renzo, Nicola; Sorà, Federica; Rege-Cambrin, Giovanna; La Nasa, Giorgio; Scortechini, Anna Rita; Greco, Giovanna; Franceschini, Luca; Sica, Simona; Bocchia, Monica; Crugnola, Monica; Orlandi, Esther; Guarini, Attilio; Specchia, Giorgina; Rosti, Gianantonio; Saglio, Giuseppe; Alimena, Giuliana
Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian "real-life" experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80 mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML. Copyright © 2015 Elsevier Ltd. All rights reserved.
The design of a high efficiency double acting piston pump suitable for pumping liquefied gases at cryogenic temperatures for cable cooling, is reported. The pump has proved flexible, reliable and efficient in operation. The plunger-type pumps can be used for filling cryostats or dewars with liquid helium or nitrogen from a pressure free or pressurized storage vessel, or as circulators for subcooled, saturated and/or supercritical helium in large scale cooling experiments. Flow rates of up to 17 g/s, maximum operating pressure of 600 kPa absolute and maximum differential pressure of approximately 100 kPa are obtained. (UK)
Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N
Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.
Owen A. Ung
Conclusions: The SNAC trial is one of the fastest accruing clinical trials in Australasia. It is on track to determine whether differences in morbidity, with equivalent cancer-related outcomes, exist between SLNB and AC for women with early breast cancer.
Baldoni, Daniela; Bruderer, Shirin; Krause, Andreas; Gutierrez, Marcello; Gueret, Pierre; Astruc, Béatrice; Dingemanse, Jasper
ACT-246475 is a new reversible, selective, and potent antagonist of the platelet P2Y12 receptor. This study was a first-in-man trial investigating the tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of ACT-246475 and its di-ester prodrug (ACT-281959) in healthy males. The study had a double-blind, randomized, ascending single-dose design with an oral formulation F1 (i.e., ACT-281959 or placebo) (Part I) and an open-label, randomized, 3-period, crossover design comparing exploratory formulations of ACT-281959 (F2) 70 mg and ACT-246475 (dF) 50 mg to F1 70 mg (Part II). In Part I, doses up to 1,000 mg were tested in 40 healthy subjects. Nine healthy subjects were enrolled in Part II. Standard safety parameters, inhibition of platelet aggregation, and ACT-246475 plasma concentrations were measured. Non-compartmental pharmacokinetic analysis was performed. All doses and formulations were well tolerated. The most frequent adverse event was headache, whereas no events of bleeding or dyspnea were reported. In Part I, ACT-246475 area under the plasma concentration-time curve (AUC) increased dose-proportionally whereas maximum plasma concentration (C max) was less than dose-proportional. The highest C max [geometric mean (95 % CI)] at 1,000 mg was 13.8 (9.7, 19.5) pmol/mL at 4.5 h post-dose, terminal half-life (t ½) was ~10 h. ACT-246475 C max and AUC0-∞ ratios of geometric means (90 % CI) using F1 as reference, for F2 were 8.5 (5.42, 13.35) and 3.4 (2.40, 4.82), respectively, and for dF 2.2 (1.42, 3.49) and 1.5 (1.07, 2.16), respectively. Mean peak platelet inhibition was 31.0 % after F1 (1,000 mg) and 47.8 % after F2. Oral doses of ACT-281959 and ACT-246475 were well tolerated. Platelet inhibition correlated with ACT-246475 exposure. Exploratory formulations enhanced the bioavailability and antiplatelet effect of ACT-246475.
Full Text Available Abstract Background The sequence of events in a behaviour change trial involves interactions between research participants and the trial process. Taking part in such a study has the potential to influence the behaviour of the participant, and if it does, this can engender bias in trial outcomes. Since participants’ experience has received scant attention, the aim of this study is thus to generate hypotheses about which aspects of the conduct of behaviour change trials might matter most to participants, and thus have potential to alter subsequent behaviours and bias trial outcomes Methods Twenty participants were opportunistically screened for a health compromising behaviour (unhealthy diet, lack of exercise, smoking or alcohol consumption and recruited if eligible. Semi structured face to face interviews were conducted, after going through the usual processes involved in trial recruitment, baseline assessment and randomisation. Participants were given information on the contents of an intervention or control condition in a behaviour change trial, which was not actually implemented. Three months later they returned to reflect on these experiences and whether they had any effect on their behaviour during the intervening period. Data from the latter interview were analysed thematically using a modified grounded theory approach. Results The early processes of trial participation raised awareness of unhealthy behaviours, although most reported having had only fleeting intentions to change their behaviour as a result of taking part in this study, in the absence of interventions. However, careful examination of the accounts revealed evidence of subtle research participation effects, which varied according to the health behaviour, and its perceived social acceptability. Participants’ relationships with the research study were viewed as somewhat important in stimulating thinking about whether and how to make lifestyle changes. Conclusion These
Brown, JP; Amaechi, BT; Bader, JD; Gilbert, GH; Makhija, SK; Lozano-Pineda, J; Leo, MC; Chuhe, C; Vollmer, WM
Objectives To better understand the effectiveness of xylitol in caries prevention in adults, and to attempt improved clinical trial efficiency. Methods As part of the Xylitol for Adult Caries Trial (X-ACT), non-cavitated and cavitated caries lesions were assessed in subjects who were experiencing the disease. The trial was a test of the effectiveness of 5 grams/day of xylitol, consumed by dissolving in the mouth five 1 gram lozenges spaced across each day, compared with a sucralose placebo. For this analysis, seeking trial efficiency, 538 subjects aged 21–80, with complete data for four dental examinations were selected from the 691 randomized into the three year trial, conducted at three sites. Acceptable inter and intra examiner reliability before and during the trial was quantified using the kappa statistic. Results The mean annualized non-cavitated plus cavitated lesion transition scores in coronal and root surfaces, from sound to carious favoured xylitol over placebo, during the three cumulative periods of 12, 24, and 33 months, but these clinically and statistically non-significant differences declined in magnitude over time. Restricting the present assessment to those subjects with a higher baseline lifetime caries experience showed possible but inconsistent benefit. Conclusions There was no clear and clinically relevant preventive effect of xylitol on caries in adults with adequate fluoride exposure when non-cavitated plus cavitated lesions were assessed. This conformed to the X-ACT trial result assessing cavitated lesions. Including non-cavitated lesion assessment in this full scale, placebo controlled, multi site, randomized, double blinded clinical trial in adults experiencing dental caries, did not achieve added trial efficiency or demonstrate practical benefit of xylitol. Trial Registration ClinicalTrials.Gov NCT00393055 PMID:24205951
Brown, John P; Amaechi, Bennett T; Bader, James D; Gilbert, Gregg H; Makhija, Sonia K; Lozano-Pineda, Juanita; Leo, Michael C; Chen, Chuhe; Vollmer, William M
To better understand the effectiveness of xylitol in caries prevention in adults and to attempt improved clinical trial efficiency. As part of the Xylitol for Adult Caries Trial (X-ACT), non cavitated and cavitated caries lesions were assessed in subjects who were experiencing the disease. The trial was a test of the effectiveness of 5 g/day of xylitol, consumed by dissolving in the mouth five 1 g lozenges spaced across each day, compared with a sucralose placebo. For this analysis, seeking trial efficiency, 538 subjects aged 21-80, with complete data for four dental examinations, were selected from the 691 randomized into the 3-year trial, conducted at three sites. Acceptable inter- and intra-examiner reliability before and during the trial was quantified using the kappa statistic. The mean annualized noncavitated plus cavitated lesion transition scores in coronal and root surfaces, from sound to carious favoured xylitol over placebo, during the three cumulative periods of 12, 24, and 33 months, but these clinically and statistically nonsignificant differences declined in magnitude over time. Restricting the present assessment to those subjects with a higher baseline lifetime caries experience showed possible but inconsistent benefit. There was no clear and clinically relevant preventive effect of xylitol on caries in adults with adequate fluoride exposure when non cavitated plus cavitated lesions were assessed. This conformed to the X-ACT trial result assessing cavitated lesions. Including non cavitated lesion assessment in this full-scale, placebo-controlled, multisite, randomized, double-blinded clinical trial in adults experiencing dental caries did not achieve added trial efficiency or demonstrate practical benefit of xylitol. ClinicalTrials.Gov NCT00393055. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Lykins, William R; Luecke, Ellen; Johengen, Daniel; van der Straten, Ariane; Desai, Tejal A
Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.
Abdulla, S.; Adam, I.; Adjei, G. O.
values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled...... trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting...... early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included...
In this presentation the new atomic act approved in the Czech republic is analyzed from the point of view of irradiation from radon and natural radiation sources in workplaces. Experience of supervision are also discussed. (authors)
Bogaerts, Annick; Ameye, Lieveke; Bijlholt, Margriet; Amuli, Kelly; Heynickx, Dorine; Devlieger, Roland
Excessive maternal pre-pregnancy and gestational weight gain are related to pregnancy- and birth outcomes. The interpregnancy time window offers a unique opportunity to intervene in order to acquire a healthy lifestyle before the start of a new pregnancy. INTER-ACT is an e-health driven multicentre randomised controlled intervention trial targeting women at high risk of pregnancy- and birth related complications. Eligible women are recruited for the study at day 2 or 3 postpartum. At week 6 postpartum, participants are randomised into the intervention or control arm of the study. The intervention focuses on weight, diet, physical activity and mental well-being, and comprises face-to-face coaching, in which behavioural change techniques are central, and use of a mobile application, which is Bluetooth-connected to a weighing scale and activity tracker. The intervention is rolled out postpartum (4 coaching sessions between week 6 and month 6) and in a new pregnancy (3 coaching sessions, one in each trimester of pregnancy); the mobile app is used throughout the two intervention phases. Data collection includes data from the medical record of the participants (pregnancy outcomes and medical history), anthropometric data (height, weight, waist- and hip circumferences, skinfold thickness and body composition by bio-electrical impedance analysis), data from the mobile app (physical activity and weight; intervention group only) and questionnaires (socio-demographics, breastfeeding, food intake, physical activity, lifestyle, psychosocial factors and process evaluation). Medical record data are collected at inclusion and at delivery of the subsequent pregnancy. All other data are collected at week 6 and month 6 postpartum and every subsequent 6 months until a new pregnancy, and in every trimester in the new pregnancy. Primary outcome is the composite endpoint score of pregnancy-induced hypertension, gestational diabetes mellitus, caesarean section, and large
Hughes, Laura S; Clark, Jodi; Colclough, Janette A; Dale, Elizabeth; McMillan, Dean
Chronic pain places a burden on individuals and the economy. Although there is evidence for the effectiveness of cognitive-behavior therapy, it is recognized that the effects are limited. Acceptance and Commitment Therapy (ACT), which aims to increase valued action in the presence of pain, has been suggested as an alternative approach. The objective of this review was to determine the clinical effectiveness of ACT for chronic pain in adults when compared with control conditions and other active treatments. The searches of this systematic review were conducted in the Cochrane library, MEDLINE, EMBASE, CINAHL Plus (EBSCO), and PsycINFO. Grey literature, reference list, and reverse citation searches were also completed. Eleven trials were included. ACT was favored over controls (no alternative intervention or treatment as usual). Significant, medium to large effect sizes were found for measures of pain acceptance and psychological flexibility, which are typically considered processes of ACT. Significant small to medium effect sizes were found for measures of functioning, anxiety, and depression. Measures of pain intensity and quality of life were not significantly different than zero. Generally effect sizes were smaller at follow-up. ACT was more clinically effective than controls on a number of outcomes. It is possible that methodological limitations, some of which are common to psychological trials, may have led to overestimated effects. Only a few studies compared ACT to active treatments and while the evidence is promising for ACT in the treatment of chronic pain, further methodologically robust trials are required.
Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua
and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016. SELECTION CRITERIA: Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic......BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate...
Full Text Available Abstract Background Despite the growing emphasis on the inclusion of ethnic minority patients in research, there is little published on the recruitment of these populations especially to randomised, community based, lifestyle intervention trials in the UK. Methods We share our experience of recruitment to screening in the PODOSA (Prevention of Diabetes and Obesity in South Asians trial, which screened 1319 recruits (target 1800 for trial eligibility. A multi-pronged recruitment approach was used. Enrolment via the National Health Service included direct referrals from health care professionals and written invitations via general practices. Recruitment within the community was carried out by both the research team and through our partnerships with local South Asian groups and organisations. Participants were encouraged to refer friends and family throughout the recruitment period. Results Health care professionals referred only 55 potential participants. The response to written invitations via general practitioners was 5.2%, lower than reported in other general populations. Community orientated, personal approaches for recruitment were comparatively effective yielding 1728 referrals (82% to the screening stage. Conclusions The PODOSA experience shows that a community orientated, personal approach for recruiting South Asian ethnic minority populations can be successful in a trial setting. We recommend that consideration is given to cover recruitment costs associated with community engagement and other personalised approaches. Researchers should consider prioritising approaches that minimise interference with professionals' work and, particularly in the current economic climate, keep costs to a minimum. The lessons learned in PODOSA should contribute to future community based trials in South Asians. Trial Registration Current Controlled Trials ISRCTN25729565
Duhamet, Jean; Lanoe, Jean-Yves; Rivalier, Patrick; Borda, Gilles
Many trials have been performed in ATALANTE's shielded cells to demonstrate the technical feasibility of processes involving minor actinide separation. They required developments of new extractors as well as a step by step procedure have been used to lower the risks of malfunction during high active operation. The design of the extractors developed by Cea has included shielded cells restrictions, miniaturization to lower the quantity of high active material and wastes and the care for being representative of industrial equipment. After individual shake down inactive tests, with actual phases, each process experiment scheduled in ATALANTE has been tested at G1 Facility in Marcoule. The objective was to reproduce as much as possible all the equipment chosen for active tests. This procedure has demonstrated its efficiency to detect many problems that would have heavy impact if they have been discovered during active trials. It was also used for operators'training. (authors)
Losada, Andrés; Márquez-González, María; Romero-Moreno, Rosa; Mausbach, Brent T; López, Javier; Fernández-Fernández, Virginia; Nogales-González, Celia
The differential efficacy of acceptance and commitment therapy (ACT) and cognitive-behavioral therapy (CBT) for dementia family caregivers' is analyzed through a randomized controlled trial. Participants were 135 caregivers with high depressive symptomatology who were randomly allocated to the intervention conditions or a control group (CG). Pre-, postintervention, and follow-up measurements assessed depressive symptomatology, anxiety, leisure, dysfunctional thoughts, and experiential avoidance. Depression: Significant effects of interventions compared with CG were found for CBT (p dementia caregivers. (c) 2015 APA, all rights reserved).
Full Text Available Prior research has demonstrated the impact of employee emotional labor strategies (deep and surface acting on customer behavioral intentions. However, there is limited data on the impact of emotional labor strategy on potential intervening variables and on actual buying decisions. This study extends the prior research by examining the effect of employee emotional labor strategies on customers’ emotional experiences and actual customer purchasing decisions. Data were collected from 294 employee-customer pairs from retail cell phone stores in China. Results indicated that choice of strategy (deep or surface does significantly impact purchase decisions. In addition, the relationship between strategy and purchase is mediated by the customer's emotional experience.
Zielinski Stephanie M
Full Text Available Abstract Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures. Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139 in the Netherlands to 232 days (P25-P75 98-423 in Canada (p = 0.027. The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21 per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28, representing 3.9% of eligible patients (p Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration ClinicalTrials.gov: NCT00761813
This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....
Mbonye, Anthony K; Magnussen, Pascal; Chandler, Clare I R; Hansen, Kristian S; Lal, Sham; Cundill, Bonnie; Lynch, Caroline A; Clarke, Siân E
An intervention was designed to introduce rapid diagnostics tests for malaria (mRDTs) into registered drug shops in Uganda to encourage rational and appropriate treatment of malaria with artemisinin-based combination therapy (ACT). We conducted participatory training of drug shop vendors and implemented supporting interventions to orientate local communities (patients) and the public sector (health facility staff and district officials) to the behavioral changes in diagnosis, treatment and referral being introduced in drug shops. The intervention was designed to be evaluated through a cluster randomized trial. In this paper, we present detailed design, implementation and evaluation experiences in order to help inform future studies of a complex nature. Three preparatory studies (formative, baseline and willingness-to-pay) were conducted to explore perceptions on diagnosis and treatment of malaria at drug shops, and affordable prices for mRDTs and ACTs in order to inform the design of the intervention and implementation modalities. The intervention required careful design with the intention to be acceptable, sustainable and effective. Critical components of intervention were: community sensitization and creating awareness, training of drug shop vendors to diagnose malaria with mRDTs, treat and refer customers to formal health facilities, giving pre-referral rectal artesunate and improved record-keeping. The primary outcome was the proportion of patients receiving appropriately-targeted treatment with ACT, evaluated against microscopy on a research blood slide. Introducing mRDTs in drug shops may seem simple, but our experience of intervention design, conduct and evaluation showed this to be a complex process requiring multiple interventions and evaluation components drawing from a combination of epidemiological, social science and health economics methodologies. The trial was conducted in phases sequenced such that each benefited from the other. The main challenges
Sharav, Vera Hassner
This article argues that contrary to the claims made by research stakeholders in industry, academia and government, the shift in public policy since the enactment of the Food and Drug Administration Modernization Act (FDAMA) of 1997 and its financial incentives to industry to test drugs on children, has had a deleterious impact on children's dignity, health and welfare. Those lucrative incentives offered an opportunity to accelerate the pace of FDA approval for pediatric drug marketing. FDAMA resulted in a radical shift in federal policy to accommodate an expansion of pediatric trials. Children who are precluded from exercising a human adult's right to informed consent to research are increasingly sought as test subjects even when the trials offer no potential benefit for them. Prior to FDAMA children were protected under federal regulations that prohibited their recruitment for experiments that were not in their best interest. This article discusses eight cases and controversies demonstrating that children have been subjected to experiments that exposed them to pain, discomfort, and serious risks of harm. Babies have died testing a lethal heartburn drug; children have been subjected to "forced dose titration" in antidepressant drug trials that resulted in several suicide attempts. Toddlers are currently being subjected to methylphenidate dose tolerance tests without evidence of any pathological condition. Healthy teenagers are being exposed to antipsychotic drugs known to induce severe pathological side effects in speculative "schizophrenia prevention" experiments.
Ephraim, Patti L; Hill-Briggs, Felicia; Roter, Debra L; Bone, Lee R; Wolff, Jennifer L; Lewis-Boyer, LaPricia; Levine, David M; Aboumatar, Hanan J; Cooper, Lisa A; Fitzpatrick, Stephanie J; Gudzune, Kimberly A; Albert, Michael C; Monroe, Dwyan; Simmons, Michelle; Hickman, Debra; Purnell, Leon; Fisher, Annette; Matens, Richard; Noronha, Gary J; Fagan, Peter J; Ramamurthi, Hema C; Ameling, Jessica M; Charlston, Jeanne; Sam, Tanyka S; Carson, Kathryn A; Wang, Nae-Yuh; Crews, Deidra C; Greer, Raquel C; Sneed, Valerie; Flynn, Sarah J; DePasquale, Nicole; Boulware, L Ebony
Given their high rates of uncontrolled blood pressure, urban African Americans comprise a particularly vulnerable subgroup of persons with hypertension. Substantial evidence has demonstrated the important role of family and community support in improving patients' management of a variety of chronic illnesses. However, studies of multi-level interventions designed specifically to improve urban African American patients' blood pressure self-management by simultaneously leveraging patient, family, and community strengths are lacking. We report the protocol of the Achieving Blood Pressure Control Together (ACT) study, a randomized controlled trial designed to study the effectiveness of interventions that engage patient, family, and community-level resources to facilitate urban African American hypertensive patients' improved hypertension self-management and subsequent hypertension control. African American patients with uncontrolled hypertension receiving health care in an urban primary care clinic will be randomly assigned to receive 1) an educational intervention led by a community health worker alone, 2) the community health worker intervention plus a patient and family communication activation intervention, or 3) the community health worker intervention plus a problem-solving intervention. All participants enrolled in the study will receive and be trained to use a digital home blood pressure machine. The primary outcome of the randomized controlled trial will be patients' blood pressure control at 12months. Results from the ACT study will provide needed evidence on the effectiveness of comprehensive multi-level interventions to improve urban African American patients' hypertension control. Copyright © 2014 Elsevier Inc. All rights reserved.
Pickler, Rita H; Wetzel, Paul A; Meinzen-Derr, Jareen; Tubbs-Cooley, Heather L; Moore, Margo
Neurobehavioral disabilities occur in 5-15% of preterm infants with an estimated 50-70% of very low birth weight preterm infants experiencing later dysfunction, including cognitive, behavioral, and social delays that often persist into adulthood. Factors implicated in poor neurobehavioral and developmental outcomes are hospitalization in the neonatal intensive care unit (NICU) and inconsistent caregiving patterns. Although much underlying brain damage occurs in utero or shortly after birth, neuroprotective strategies can stop lesions from progressing, particularly when these strategies are used during the most sensitive periods of neural plasticity occurring months before term age. The purpose of this randomized trial is to test the effect of a patterned feeding experience on preterm infants' neurobehavioral organization and development, cognitive function, and clinical outcomes. This trial uses an experimental, longitudinal, 2-group design with 120 preterm infants. Infants are enrolled within the first week of life and randomized to an experimental group receiving a patterned feeding experience from the first gavage feeding through discharge or to a control group receiving usual feeding care experience. The intervention involves a continuity of tactile experiences associated with feeding to train and build neuronal networks supportive of normal infant feeding experience. Primary outcomes are neurobehavioral organization as measured by Neurobehavioral Assessment of the Preterm Infant at 3 time points: the transition to oral feedings, NICU discharge, and 2 months corrected age. Secondary aims are cognitive function measured using the Bayley Scales of Infant and Toddler Development, Third Edition at 6 months corrected age, neurobehavioral development (sucking organization, feeding performance, and heart rate variability), and clinical outcomes (length of NICU stay and time to full oral feeding). The potential effects of demographic and biobehavioral factors
Full Text Available Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs, have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of
Full Text Available Abstract Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16, three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender. Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022 and enhanced mood (p=.027. The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin
Bekelis, Kimon; Calnan, Daniel; Simmons, Nathan; MacKenzie, Todd A; Kakoulides, George
To investigate the effect of exposure to a virtual reality (VR) environment preoperatively on patient-reported outcomes for surgical operations. There is a scarcity of well-developed quality improvement initiatives targeting patient satisfaction. We performed a randomized controlled trial of patients undergoing cranial and spinal operations in a tertiary referral center. Patients underwent a 1:1 randomization to an immersive preoperative VR experience or standard preoperative experience stratified on type of operation. The primary outcome measures were the Evaluation du Vecu de l'Anesthesie Generale (EVAN-G) score and the Amsterdam Preoperative Anxiety and Information (APAIS) score, as markers of the patient's experience during the surgical encounter. During the study period, a total of 127 patients (mean age 55.3 years, 41.9% females) underwent randomization. The average EVAN-G score was 84.3 (standard deviation, SD, 6.4) after VR, and 64.3 (SD, 11.7) after standard preoperative experience (difference, 20.0; 95% confidence interval, CI, 16.6-23.3). Exposure to an immersive VR experience also led to higher APAIS score (difference, 29.9; 95% CI, 24.5-35.2). In addition, VR led to lower preoperative VAS stress score (difference, -41.7; 95% CI, -33.1 to -50.2), and higher preoperative VAS preparedness (difference, 32.4; 95% CI, 24.9-39.8), and VAS satisfaction (difference, 33.2; 95% CI, 25.4-41.0) scores. No association was identified with VAS stress score (difference, -1.6; 95% CI, -13.4 to 10.2). In a randomized controlled trial, we demonstrated that patients exposed to preoperative VR had increased satisfaction during the surgical encounter. Harnessing the power of this technology, hospitals can create an immersive environment that minimizes stress, and enhances the perioperative experience.
Fullerton, Birgit; Siebenhofer, Andrea; Jeitler, Klaus; Horvath, Karl; Semlitsch, Thomas; Berghold, Andrea; Plank, Johannes; Pieber, Thomas R; Gerlach, Ferdinand M
Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes. We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant. Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in
Russell, James A; Lee, Terry; Singer, Joel; Boyd, John H; Walley, Keith R
The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L. Retrospective analysis of randomized controlled trial. Multicenter ICUs. We compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L. Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine. Concealed vasopressin (0.03 U/min.) or norepinephrine infusions. The Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L. The Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic
Michael P. Bogenschutz
Full Text Available After a hiatus of some 40 years, clinical research has resumed on the use of classic hallucinogens to treat addiction. Following completion of a small open-label feasibility study, we are currently conducting a double-blind placebo-controlled clinical trial of psilocybin-assisted treatment of alcohol use disorder. Although treatment effects cannot be analyzed until the study is complete, descriptive case studies provide a useful window into the therapeutic process of psychedelic-assisted treatment of addiction. Here we describe treatment trajectories of three participants in the ongoing trial to illustrate the range of experiences and persisting effects of psilocybin treatment. Although it is difficult to generalize from a few cases, several qualitative conclusions can be drawn from the data presented here. Although participants often find it difficult to describe much of their psilocybin experience, pivotal moments tend to be individualized, extremely vivid, and memorable. Often, the qualitative content extends beyond the clinical problem that is being addressed. The participants discussed in this paper experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol and drinking. In these cases, experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased “spaciousness” or mindfulness, and increased control over choices and behavior were reported following the drug administration sessions. Ultimately, psilocybin-assisted treatment appears to elicit experiences that are extremely variable, yet seem to meet the particular needs of the individual.
Bogenschutz, Michael P; Podrebarac, Samantha K; Duane, Jessie H; Amegadzie, Sean S; Malone, Tara C; Owens, Lindsey T; Ross, Stephen; Mennenga, Sarah E
After a hiatus of some 40 years, clinical research has resumed on the use of classic hallucinogens to treat addiction. Following completion of a small open-label feasibility study, we are currently conducting a double-blind placebo-controlled clinical trial of psilocybin-assisted treatment of alcohol use disorder. Although treatment effects cannot be analyzed until the study is complete, descriptive case studies provide a useful window into the therapeutic process of psychedelic-assisted treatment of addiction. Here we describe treatment trajectories of three participants in the ongoing trial to illustrate the range of experiences and persisting effects of psilocybin treatment. Although it is difficult to generalize from a few cases, several qualitative conclusions can be drawn from the data presented here. Although participants often find it difficult to describe much of their psilocybin experience, pivotal moments tend to be individualized, extremely vivid, and memorable. Often, the qualitative content extends beyond the clinical problem that is being addressed. The participants discussed in this paper experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol and drinking. In these cases, experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased "spaciousness" or mindfulness, and increased control over choices and behavior were reported following the drug administration sessions. Ultimately, psilocybin-assisted treatment appears to elicit experiences that are extremely variable, yet seem to meet the particular needs of the individual.
Pinto Dos Santos, Daniel; Arnhold, Gordon; Mildenberger, Peter; Düber, Christoph; Kloeckner, Roman
the German Transplantation Act - Initial Experiences with Structured Reporting. Fortschr Röntgenstr 2017; 189: 1145 - 1151. © Georg Thieme Verlag KG Stuttgart · New York.
Sajatovic, Martha; Levin, Jennifer; Ramirez, Luis F; Hahn, David Y; Tatsuoka, Curtis; Bialko, Christopher S; Cassidy, Kristin A; Fuentes-Casiano, Edna; Williams, Tiffany D
Treatment nonadherence in people with schizophrenia is associated with relapse and homelessness. Building on the usefulness of long-acting medication and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with DSM-IV-defined schizophrenia or schizoaffective disorder. Participants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence, as measured by the Tablets Routine Questionnaire, and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. The study was conducted from July 2010 to December 2012. The mean age of participants was 41.8 years (SD = 8.6); they were mainly minorities (90%, n = 27 African-American) and mainly single/never married (70%, n = 21). Most (97%, n = 29) had past or current substance abuse and had been incarcerated (97%, n = 29). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (at 6 months, 76%) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (P = .03). There were significant improvements in psychiatric symptoms (P effect with LAI. While interpretation of findings must be tempered by the methodological limitations, CAE-L appears to be associated with improved adherence, symptoms, and functioning in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness. ClinicalTrials.gov identifier: NCT01152697. © Copyright 2013 Physicians Postgraduate Press, Inc.
Kelly, Thomas M; Daley, Dennis C; Byrne, Mimmie; Demarzo, Larry; Smith, Doris; Madl, Stephanie
The National Institute on Drug Abuse (NIDA)-sponsored Clinical Trial Network (CTN) recently celebrated 10 years of conducting "real world" research into the treatment of addiction. This article reviews the history and results of the most recent CTN studies and describes the experiences of one of the 13 participating research affiliates, the Appalachian Tri-State (ATS) Node. We discuss our "bidirectional" collaboration with multiple community treatment programs (CTPs) on research and dissemination activities and include their experiences as a member of our ATS Node.Results of CTN clinical trials have found unexpectedly that treatment as usual (TAU) is often almost as good as evidence-based interventions such as Motivational Interviewing (MI), possibly due to the difficulty in implementing evidence-based practices most effectively among divergent treatment sites and heterogeneous clinical populations. Some expected findings from the reviewed research are that severity of addiction and comorbidity moderate treatment outcomes and must be accounted for in future CTN-sponsored studies. Notwithstanding these results, much has been learned and recommendations are suggested for changes in CTN research designs that will address methodological limitations and increase treatment effectiveness in future CTN studies.
Haridy, James; Wigg, Alan; Muller, Kate; Ramachandran, Jeyamani; Tilley, Emma; Waddell, Victoria; Gordon, David; Shaw, David; Huynh, Dep; Stewart, Jeffrey; Nelson, Renjy; Warner, Morgyn; Boyd, Mark; Chinnaratha, Mohamed A; Harding, Damian; Ralton, Lucy; Colman, Anton; Liew, Danny; Iyngkaran, Guru; Tse, Edmund
In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve-months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, p=0.03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, p=0.03) and younger age (OR 0.98, 95% CI 0.97-0.99, p=0.05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23,95% CI 0.07-0.74, p=0.01) and genotype 3 (OR 0.23 95% CI 0.12-0.43, p=<0.01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials, however a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlights the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Full Text Available Abstract Background Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment. Methods The Estonian Postmenopausal Hormone Therapy trial (EPHT, originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT on health services utilization. Results After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT. Conclusion Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials. The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old drug for a new preventive indication? In preventive drug trials companies may
Full Text Available Abstract Background A new intervention aimed at managing patients with medically unexplained symptoms (MUS based on a specific set of communication techniques was developed, and tested in a cluster randomised clinical trial. Due to the modest results obtained and in order to improve our intervention we need to know the GPs' attitudes towards patients with MUS, their experience, expectations and the utility of the communication techniques we proposed and the feasibility of implementing them. Physicians who took part in 2 different training programs and in a randomised controlled trial (RCT for patients with MUS were questioned to ascertain the reasons for the doctors' participation in the trial and the attitudes, experiences and expectations of GPs about the intervention. Methods A qualitative study based on four focus groups with GPs who took part in a RCT. A content analysis was carried out. Results Following the RCT patients are perceived as true suffering persons, and the relationship with them has improved in GPs of both groups. GPs mostly valued the fact that it is highly structured, that it made possible a more comfortable relationship and that it could be applied to a broad spectrum of patients with psychosocial problems. Nevertheless, all participants consider that change in patients is necessary; GPs in the intervention group remarked that that is extremely difficult to achieve. Conclusion GPs positively evaluate the communication techniques and the interventions that help in understanding patient suffering, and express the enormous difficulties in handling change in patients. These findings provide information on the direction in which efforts for improving intervention should be directed. Trial registration US ClinicalTrials.gov NCT00130988
Mngadi, Kathryn Therese; Frohlich, Janet; Montague, Carl; Singh, Jerome; Nkomonde, Nelisiwe; Mvandaba, Nomzamo; Ntombeka, Fanelesibonge; Luthuli, Londiwe; Abdool Karim, Quarraisha; Mansoor, Leila
Reimbursement of trial participants remains a frequently debated issue, with specific guidance lacking. Trials combining post-trial access and implementation science may necessitate new strategies and models. CAPRISA 008, a post-trial access study testing the feasibility of using family planning services to rollout a prelicensure HIV prevention intervention, tried to balance the real-life scenario of no reimbursement for attendance at public sector clinics with that of a trial including some visits that focused on research procedures and others that focused on standard of care procedures. A reduced reimbursement was offered for 'standard of care' visits, meant primarily to cover transport costs to and from the clinic only. This impacted negatively on accrual, retention and participant morale, primarily due to the protracted delay in regulatory approval, during which time, the costs of living, including travel costs had increased. Relevant guidelines were reviewed and institutional policy was updated to incorporate the South African National Health Research Ethics Committee guidelines on reimbursement (taking into account participant time, travel and inconvenience). The reimbursement amount for 'standard of care' visits was increased accordingly. The question remains whether a trial that combines post-trial access with implementation science, with clear benefits for the participants and the provision of above standard medical care, should have reimbursement rates that approach those of a proof-of-concept trial, for 'standard of care' visits. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Arden-Close, E; Yardley, L; Kirby, S; Thomas, M; Bruton, A
Poor symptom control and impaired quality of life are common in adults with asthma, and breathing retraining exercises may be an effective method of self-management. This study aimed to explore the experiences of participants in the intervention arms of the BREATHE trial, which investigated the effectiveness of breathing retraining as a mode of asthma management. Sixteen people with asthma (11 women, 8 per group) who had taken part in the intervention arms of the BREATHE trial (breathing retr...
The German research reactors FRG-1 and FRG-2 have passed different types of licensing procedures in the past years. It is reported about the experiences we have got in the interpretation and application of section 7 of the German Atomic Energy Act. Following these experiences an estimation is done for the licensing procedure for the reduction of the uranium enrichment. (orig.) [de
been met with denial, procrastination and bungling. From a public health point of view this has been a disaster. Will we again miss the chance to act decisively when it comes to perinatal transmission? For African scientists to try to politicise criticism of placebo trials as intervention from the. West is wrong. Rather, they must ...
Scardino Peter T
Full Text Available Abstract Introduction Randomized controlled trials provide the best method of determining which of two comparable treatments is preferable. Unfortunately, contemporary randomized trials have become increasingly expensive, complex and burdened by regulation, so much so that many trials are of doubtful feasibility. Discussion Here we present a proposal for a novel, streamlined approach to randomized trials: the "clinically-integrated randomized trial". The key aspect of our methodology is that the clinical experience of the patient and doctor is virtually indistinguishable whether or not the patient is randomized, primarily because outcome data are obtained from routine clinical data, or from short, web-based questionnaires. Integration of a randomized trial into routine clinical practice also implies that there should be an attempt to randomize every patient, a corollary of which is that eligibility criteria are minimized. The similar clinical experience of patients on- and off-study also entails that the marginal cost of putting an additional patient on trial is negligible. We propose examples of how the clinically-integrated randomized trial might be applied in four distinct areas of medicine: comparisons of surgical techniques, "me too" drugs, rare diseases and lifestyle interventions. Barriers to implementing clinically-integrated randomized trials are discussed. Conclusion The proposed clinically-integrated randomized trial may allow us to enlarge dramatically the number of clinical questions that can be addressed by randomization.
Full Text Available Abstract Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA. The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients’ experiences, and stakeholders’ experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first
Grøthe, Å; Biong, Stian; Grov, E K
Admission of a cancer patient to a palliative unit when near the final stage of their disease trajectory undoubtedly impacts their relatives. The aim of our study was to illuminate and interpret relatives' lived experiences of health personnel's provision of care in a palliative ward. A phenomenological/hermeneutic approach was employed that was inspired by the philosophical tradition of Heidegger and Ricoeur and further developed by Lindseth and Nordberg. The perspectives of the narrator and the text were interpreted by highlighting relatives' views on a situation in which they have to face existential challenges. The analysis was undertaken in three steps: naïve reading, structural analysis, and comprehensive understanding, including the authors' professional experiences and theoretical background. Six subthemes appeared: the dying person, the bubble, the sight, the cover, the provision for children's needs, and the availability of immediate help. These components were further constructed into three themes: the meaning of relating, the meaning of action, and the meaning of resources. Our comprehensive understanding of the results suggests that the most important theme is "acting with dedication and expertise." The following aspects are crucial for relatives of cancer patients hospitalized in a palliative ward: time and existence, family dynamics, and care adjusted to the situation. Our study results led to reflections on the impact of how nurses behave when providing care to patients during the palliative phase, and how they interact with relatives in this situation. We found that cancer patients in a palliative unit most appreciate nurses who act with dedication and expertise.
It is recommended that more recognition be given to the important role of trial counsellors in clinical trials, and that they be given more formal training, support and ... Daar word aanbeveel dat meer erkenning gegee word aan die rol van proefvoorligters in kliniese proewe, dat hulle meer formele opleiding ondergaan, dat ...
Laranjeira, Fernanda O; de Andrade, Keitty R C; Figueiredo, Ana C M G; Silva, Everton N; Pereira, Mauricio G
The comparison between long acting insulin analogues (LAIA) and human insulin (NPH) has been investigated for decades, with many randomized controlled trials (RCTs) and systematic reviews giving mixed results. This overlapping and contradictory evidence has increased uncertainty on coverage decisions at health systems level. To conduct an overview of systematic reviews and update existing reviews, preparing new meta-analysis to determine whether LAIA are effective for T1D patients compared to NPH. We identified systematic reviews of RCTs that evaluated the efficacy of LAIA glargine or detemir, compared to NPH insulin for T1D, assessing glycated hemoglobin (A1C) and hypoglycemia. Data sources included Pubmed, Cochrane Library, EMBASE and hand-searching. The methodological quality of studies was independently assessed by two reviewers, using AMSTAR and Jadad scale. We found 11 eligible systematic reviews that contained a total of 25 relevant clinical trials. Two reviewers independently abstracted data. We found evidence that LAIA are efficacious compared to NPH, with estimates showing a reduction in nocturnal hypoglycemia episodes (RR 0.66; 95% CI 0.57; 0.76) and A1C (95% CI 0.23; 0.12). No significance was found related to severe hypoglycemia (RR 0.94; 95% CI 0.71; 1.24). This study design has allowed us to carry out the most comprehensive assessment of RCTs on this subject, filling a gap in diabetes research. Our paper addresses a question that is important not only for decision makers but also for clinicians.
van Gijn, J
From the age of Enlightenment onwards, philosophical thinking has become increasingly influenced by empiricism: observations lead to theories, but experiments are needed to put the reasoning to the test. However, it was not until the middle of the 20th century that well-designed experiments were at last introduced in medical treatment, in the form of randomised controlled clinical trials. This design is now standard in medicine, but in everyday practice a multitude of management decisions must still be taken without good evidence. There are several reasons for this: there may not be a trial at all or only a single trial; trial results may be equivocal; patients may be different from those enrolled in trials; new procedures require practice, or a trial may not be feasible. 'Logical reasoning', with all its fallacies, is still required - not only to fill the gaps in empirical knowledge but also to interpret existing evidence and to plan new trials. In fact, the generation of new knowledge is a continuous, cyclical process in which newly gained insights in pathophysiology give rise to new therapeutic experiments, the results of which generate fresh hypotheses, and so on. Compassion, curiosity and doubt are the essential forces that keep the cycle moving. Conversely, the progress is slowed down by present-day legalism, which distorts investigator accountability and patient autonomy. Copyright (c) 2005 S. Karger AG, Basel.
First page Back Continue Last page Overview Graphics. ACTS – SUCCESS STORY. Totally 103 experiments were conducted and the programme succeeded in the areas. Medicine; Education; Defence; Emergency Response; Maritime and Aeronautical Mobile Communications; Science and Astronomy.
van den Wijngaard, L; Rodijk, I C M; van der Veen, F; Gooskens-van Erven, M H W; Koks, C A M; Verhoeve, H R; Mol, B W J; van Wely, M; Mochtar, M H
What factors or attributes of a long-acting recombinant FSH (rFSH) or daily-administrated rFSH influence women's preferences IVF? Patients' preferences for rFSH products are primary influenced by the attribute 'number of injections', but a low 'number of injections' is exchanged for a high 'number of injections' at a 6.2% decrease in 'risk of cycle cancellation due to low response' and at a 4.5% decrease in 'chance of OHSS'. Injections of long-acting rFSH have been claimed to be preferred over daily-administrated rFSH injections, but patient preference studies to underpin this assumption have not been performed. A discrete choice experiment (DCE) was created to assess women's preference for long-acting or daily-administrated rFSH under varying attributes of efficiency, safety and burden. The selected attributes were the 'total number of injections', 'chance of ovarian hyperstimulation syndrome (OHSS)' and the 'risk of cycle cancellation due to low response'. Questionnaires were handed out during information gathering sessions in one academic hospital and two teaching hospitals in The Netherlands between April 2011 and April 2012. Women at the start of their first IVF treatment were asked to participate in this patient preference study. Participation was voluntary. We analysed the data by using mixed logit models to estimate the utility of each attribute. Questionnaires (n = 125) were handed out with a response rate of 77% (97/125). Four respondents did not complete the questionnaire. Hence, there were 93 questionnaires available for analysis. All attributes significantly influenced women's preference. Overall, the lower 'number of injections' was preferred above the higher 'number of injections' (mean coefficient 1.25; P lower 'number of injections' for a higher 'number of injections' when gaining a 6.2% reduction in 'cycle cancellation due to low response', or a 4.5% reduction in 'chance of OHSS'. The generalizability of this DCE is limited in time-span. Women may
Ebert, Martin A.; Haworth, Annette; Kearvell, Rachel; Hooton, Ben; Coleman, Rhonda; Spry, Nigel; Bydder, Sean; Joseph, David
Aim: Contemporary radiotherapy clinical trials typically require complex three-dimensional (3D) treatment planning. This produces large amounts of data relating technique and dose delivery for correlation with patient outcomes. Assessment of the quality of this information is required to ensure protocol compliance, to quantify the variation in treatments given to patients and to enhance the power of studies to determine correlates of patient outcomes. Materials and methods: A software system ('SWAN') was developed to facilitate the objective analysis, quality-assurance and review of digital treatment planning data from multi-centre radiotherapy trials. The utility of this system was assessed on the basis of its functionality and our experience of its use in the context of multi-centre clinical trials and trials-support activities. Results: The SWAN system has been shown to have the functionality required for use in several multi-centre trials, including automated review and archive processes. Approximately 800 treatment plans from over 30 participating institutions have so far been assessed with the system for several treatment planning scenarios. To illustrate this we include a description of the use of the system for a large-recruitment prostate radiotherapy trial being undertaken in Australasia, including examples of how the review process has changed clinical practice. Conclusion: The successful implementation of SWAN has been demonstrated in a number of clinical trials. The software provides an opportunity for comprehensive review of treatment parameters that could impact on clinical outcomes and trial results. Such quality-assurance (QA) has previously been difficult or impossible to achieve, particularly for a clinical trial involving large numbers of patients. Such reviews have highlighted inconsistencies in clinical practice that have since been addressed through feedback from the review process. The process of data collection and review should be
Meeinkuirt, Weeradej; Pokethitiyook, Prayad; Kruatrachue, Maleeya; Tanhan, Phanwimol; Chaiyarat, Rattanawat
The potential of 6 tree species (Leucaena leucocephala, Acacia mangium, Peltophorum pterocarpum, Pterocarpus macrocarpus, Lagerstroemia floribunda, Eucalyptus camaldulensis) for phytoremediation of Pb in sand tailings (total Pb >9850 mg kg(-1)) from KEMCO Pb mine in Kanchanaburi province, Thailand, were investigated employing a pot experiment (3 months) and field trial experiment (12 months). In pot study E. camaldulensis treated with Osmocote fertilizer attained the highest total biomass (15.3 g plant(-1)) followed by P. pterocarpum (12.6 g plant(-1)) and A. mangium (10.8 g plant(-1)) both treated with cow manure. Cow manure application resulted in the highest root Pb accumulation (>10000 mg kg(-1)) in L. floribunda and P. macrocarpus. These two species also exhibited the highest Pb uptake (85-88 mg plant(-1)). Results from field trial also showed that Osmocote promoted the best growth performance in E. camaldulensis (biomass 385.7 g plant(-1), height 141.7 cm) followed by A. mangium (biomass 215.9 g plant(-1), height 102.7 cm), and they also exhibited the highest Pb uptake (600-800 microg plant(-1)). A. mangium with the addition of organic fertilizer was the best option for phytostabilization of Pb-contaminated mine tailing because it retained higher Pb concentration in the roots.
Burgess, L J; Sulzer, N
The use of retention gifts in clinical trials has been controversial, with some ethicists maintaining that such gifts represent undue inducement to the trial participants. A study was conducted at TREAD Research, a site-managed organisation based at Tygerberg Hospital, in which 302 participants completed a questionnaire that focused on their opinion with regard to such gifts. The results suggest that these gifts do not influence patients to participate in a clinical trial or influence them to remain on a trial should they wish to withdraw. However, they do act as a useful motivational tool and trial participants appreciate them.
de Laat, Sonya; Schwartz, Lisa
Introduction Prospective informed consent is required for most research involving human participants; however, this is impracticable under some circumstances. The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS) outlines the requirements for research involving human participants in Canada. The need for an exception to consent (deferred consent) is recognised and endorsed in the TCPS for research in individual medical emergencies; however, little is known about substitute decision-maker (SDM) experiences. A paediatric resuscitation trial (SQUEEZE) (NCT01973907) using an exception to consent process began enrolling at McMaster Children's Hospital in January 2014. This qualitative research study aims to generate new knowledge on SDM experiences with the exception to consent process as implemented in a randomised controlled trial. Methods and analysis The SDMs of children enrolled into the SQUEEZE pilot trial will be the sampling frame from which ethics study participants will be derived. Design: Qualitative research study involving individual interviews and grounded theory methodology. Participants: SDMs for children enrolled into the SQUEEZE pilot trial. Sample size: Up to 25 SDMs. Qualitative methodology: SDMs will be invited to participate in the qualitative ethics study. Interviews with consenting SDMs will be conducted in person or by telephone, taped and professionally transcribed. Participants will be encouraged to elaborate on their experience of being asked to consent after the fact and how this process occurred. Analysis: Data gathering and analysis will be undertaken simultaneously. The investigators will collaborate in developing the coding scheme, and data will be coded using NVivo. Emerging themes will be identified. Ethics and dissemination This research represents a rare opportunity to interview parents/guardians of critically ill children enrolled into a resuscitation trial without their knowledge or prior consent
Ayers, Susan; Sawyer, Alex; Chhoa, Celine; Pushpa-Rajah, Angela; Duley, Lelia
Background\\ud Recruitment to trials when birth is imminent requires offering consent at a difficult and stressful time, often with limited time. The Cord Pilot Trial assessed timing of cord clamping at very preterm birth. To ensure high risk women were not excluded we developed a two stage oral assent pathway, for use when birth was imminent. A third of women were recruited using this pathway. The aim of this study was to explore clinicians’ and women’s’ experiences of the two consent pathway...
Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef
Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.
Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.
Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352
Tugwell-Allsup, J; Pritchard, A W
This paper reports qualitative findings from within a larger randomised control trial where a video clip or telephone conversation with a radiographer was compared to routine appointment letter and information sheet to help alleviate anxiety prior to their MRI scan. Questionnaires consisting of three free-text response questions were administered to all of the 74 patients recruited to the MRI anxiety clinical trial. The questionnaire was designed to establish patients' experiences of the intervention they had received. These questionnaires were administered post-scan. Two participants from each trial arm were also interviewed. A thematic approach was utilised for identifying recurrent categories emerging from the qualitative data which are supported by direct quotations. Participants in the interventional groups commented positively about the provision of pre-MRI scan information they received and this was contrastable with the relatively indifferent responses observed among those who received the standard information letter. Many important themes were identified including the patients needs for clear and simplified information, the experience of anticipation when waiting for the scan, and also the informally acquired information about having an MRI scan i.e. the shared experiences of friends and family. All themes highlighted the need for an inclusive and individually tailored approach to pre-scan information provision. Qualitative data collected throughout the trial is supportive of the statistical findings, where it is asserted that the use of a short video clip or a radiographer having a short conversation with patients before their scan reduces pre-scan anxiety. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
The review of the Act has progressed in stages. The first stage was conducted by the staff of the Atomic Energy Control Board (AECB) and catalogued previously identified difficulties with the Act. The second stage was a preliminary examination of the Act by an Interdepartmental Working Group (IWG). The IWG was formed in 1982 at the direction of the President of the AECB. It was instructed to review all matters relating to the administration of, and experience with, the Act and to examine these matters in as much detail as was required to resolve each point raised during the review. The IWG was composed of representatives of the AECB (which administers the Act), the Department of Energy, Mines and Resources, the Department of Finance, the Department of Insurance, the Department of Justice, and the Treasury Board Secretariat
Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B
This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise. Most chapters have been revised considerably from the fourth edition. A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded. Many contemporary clinical trial examples have been added. There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials. This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...
Agard, A; Hermeren, G; Herlitz, J
OBJECTIVE—To investigate how patients included in trials on treatment in the early phase of acute myocardial infarction experience the consent procedure. DESIGN—A combined qualitative and quantitative interview concerning the patients' knowledge of the trial, their feelings about being asked to participate, and their attitudes towards the consent procedure. SETTING—Tertiary referral centre. PATIENTS—31 patients who had given written informed consent for their participation in randomised inter...
van der Wal Gerrit
Full Text Available Abstract Background Diagnostic error is an important error type since diagnostic adverse events are regularly judged as being preventable and the consequences are considered to be severe. Existing research often focuses on either diagnostic adverse events or on the errors in diagnostic reasoning. Whether and when an incorrect diagnostic process results in adverse outcomes has not been studied extensively. The present paper describes the design of a study that aims to study the relationship between a suboptimal diagnostic process and patient outcomes. In addition, the role of personal and circumstantial factors on the quality of the diagnostic process will be examined. Methods/Design The research questions were addressed using several data sources. First, the differential diagnosis was assessed concurrently to the diagnostic process. Second, the patient records of 248 patients suffering from shortness of breath were reviewed by expert internists in order to reveal suboptimal cognitive acts and (potential consequences for the patient. The suboptimal cognitive acts were discussed with the treating physicians and classified with the taxonomy of unsafe acts. Third, workload, fatigue and work experience were measured during the physicians work. Workload and fatigue were measured during the physicians shift using the NASA tlx questionnaire on a handheld computer. Physicians participating in the study also answered questions about their work experience. Discussion The design used in this study provides insight into the relationship between suboptimal cognitive acts in the diagnostic process and possible consequences for the patient. Suboptimal cognitive acts in the diagnostic process and its causes can be revealed. Additional measurements of workload, fatigue and experience allow examining the influence of these factors on the diagnostic process. In conclusion, the present design provides a method with which insights in weaknesses of the diagnostic
Full Text Available Abstract Background Microinsurance or Community-Based Health Insurance is a promising healthcare financing mechanism, which is increasingly applied to aid rural poor persons in low-income countries. Robust empirical evidence on the causal relations between Community-Based Health Insurance and healthcare utilisation, financial protection and other areas is scarce and necessary. This paper contains a discussion of the research design of three Cluster Randomised Controlled Trials in India to measure the impact of Community-Based Health Insurance on several outcomes. Methods/Design Each trial sets up a Community-Based Health Insurance scheme among a group of micro-finance affiliate families. Villages are grouped into clusters which are congruous with pre-existing social groupings. These clusters are randomly assigned to one of three waves of implementation, ensuring the entire population is offered Community-Based Health Insurance by the end of the experiment. Each wave of treatment is preceded by a round of mixed methods evaluation, with quantitative, qualitative and spatial evidence on impact collected. Improving upon practices in published Cluster Randomised Controlled Trial literature, we detail how research design decisions have ensured that both the households offered insurance and the implementers of the Community-Based Health Insurance scheme operate in an environment replicating a non-experimental implementation. Discussion When a Cluster Randomised Controlled Trial involves randomizing within a community, generating adequate and valid conclusions requires that the research design must be made congruous with social structures within the target population, to ensure that such trials are conducted in an implementing environment which is a suitable analogue to that of a non-experimental implementing environment.
Arya, Vikram; Au, Stanley; Belew, Yodit; Miele, Peter; Struble, Kimberly
To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals (ARVs) for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately. Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication. For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug.
Full Text Available HIV vaccine trials generally require that pregnant women are excluded from participation, and contraceptive methods must be used to prevent pregnancy during the trial. However, access to quality services and misconceptions associated with contraceptive methods may impact on their effective use in developing countries. We describe the pattern of contraceptive use in a multi-site phase I/IIa HIV Vaccine trial in East Africa (Uganda, Kenya and Tanzania and factors that may have influenced their use during the trial.Pregnancy prevention counseling was provided to female participants during informed consent process and at each study visit. Participants' methods of contraception used were documented. Methods of contraceptives were provided on site. Pregnancy testing was done at designated visits during the trial. Obstacles to contraceptive use were identified and addressed at each visit.Overall, 103 (31.8% of a total of 324 enrolled volunteers were females. Female participants were generally young with a mean age of 29(+/-7.2, married (49.5% and had less than high school education (62.1%. Hormonal contraceptives were the most common method of contraception (58.3% followed by condom use (22.3%. The distribution of methods of contraception among the three sites was similar except for more condom use and less abstinence in Uganda. The majority of women (85.4% reported to contraceptive use prior to screening. The reasons for not using contraception included access to quality services, insufficient knowledge of certain methods, and misconceptions.Although hormonal contraceptives were frequently used by females participating in the vaccine trial, misconceptions and their incorrect use might have led to inconsistent use resulting in undesired pregnancies. The study underscores the need for an integrated approach to pregnancy prevention counseling during HIV vaccine trials.ClinicalTrials.gov NCT00123968.
Yamazaki, Hiroshi; Kitamura, Toshikatus; Mizushima, Toshihiko
The sea trial of the first Japan nuclear Ship 'MUTSU' was conducted from the end of October to December in 1990. The purpose of the sea trial was to verify the nuclear propulsive performances and maneuverabilities. The present report describes the results of the sea trial. These results are classified into four items: 1. Speed test and engineering performance tests 2. Maneuvering performance tests 3. Vibration tests 4. Other tests. Acceptable performances were demonstrated, as expected in the original design. The experience of the use of the Global Positioning System (GPS), which were newly adopted for the sea trial, is also reported. (author)
A prospective trial of customized adherence enhancement plus long-acting injectable antipsychotic medication in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder
Sajatovic, Martha; Levin, Jennifer; Ramirez, Luis F.; Hahn, David Y.; Tatsuoka, Curtis; Bialko, Christopher S.; Cassidy, Kristin A.; Fuentes-Casiano, Edna; Williams, Tiffany D.
Background Treatment non-adherence in people with schizophrenia is associated with relapse and homelessness. Building upon the usefulness of long-acting medication, and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with schizophrenia and schizoaffective disorder. Methods Participants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence as measured by the Tablets Routine Questionnaire (TRQ) and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. Results Mean age of participants was 41.8 years (SD 8.6), mainly minorities (90% African-American) and mainly single/never married (70%). Most (97%) had past or current substance abuse, and had been incarcerated (97%). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (76% at 6 months) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (p = 0.03). There were significant improvements in psychiatric symptoms (pschizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness. PMID:24434094
This paper expands on some of the points made by Deepak Natarajan on techniques used in designing clinical trials of new drugs to ensure favourable outcomes. It also considers the nexus between the manufacturers of new drugs and the publishers of medical journals in which edited versions of these favourable outcomes are presented to the medical fraternity. The argument will be illustrated by referring to the clinical trials of rofecoxib (Vioxx®) and etoricoxib (Arcoxia®). Both these drugs are COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) manufactured by Merck and Co. Because of the unparalleled access to Merck's internal confidential documents, due to the subpoenaing of these documents by government and private individuals in civil and criminal actions, we are still learning about the company's unconscionable acts. What we learn can inform our judgement concerning published reports of both new and old drugs.
Arden-Close, Emily; Yardley, Lucy; Kirby, Sarah; Thomas, Mike; Bruton, Anne
Poor symptom control and impaired quality of life are common in adults with asthma, and breathing retraining exercises may be an effective method of self-management. This study aimed to explore the experiences of participants in the intervention arms of the BREATHE trial, which investigated the effectiveness of breathing retraining as a mode of asthma management. Sixteen people with asthma (11 women, 8 per group) who had taken part in the intervention arms of the BREATHE trial (breathing retraining delivered by digital versatile disc (DVD) or face-to-face sessions with a respiratory physiotherapist) took part in semi-structured telephone interviews about their experiences. Interviews were analysed using thematic analysis. Breathing retraining was perceived positively as a method of asthma management. Motivations for taking part included being asked, to enhance progress in research, to feel better/reduce symptoms, and to reduce medication. Participants were positive about the physiotherapist, liked having the materials tailored, found meetings motivational, and liked the DVD and booklet. The impact of breathing retraining following regular practice included increased awareness of breathing and development of new habits. Benefits of breathing retraining included increased control over breathing, reduced need for medication, feeling more relaxed, and improved health and quality of life. Problems included finding time to practice the exercises, and difficulty mastering techniques. Breathing retraining was acceptable and valued by almost all participants, and many reported improved wellbeing. Face to face physiotherapy was well received. However, some participants in the DVD group mentioned being unable to master techniques. PATIENTS RECEPTIVE TO BREATHING RETRAINING: Patients with asthma taught how to change their unconscious breathing patterns generally like non-pharmacological interventions. Researchers in the UK, led by Mike Thomas from the University of Southampton
Lundgaard, Mette; Rabøl, Louise; Jensen, Elisabeth Agnete Brøgger
This paper describes the process that lead to the passing of the Act for Patient Safety in the Danisk health care sytem, the contents of the act and how the act is used in the Danish health care system. The act obligates frontline health care personnel to report adverse events, hospital owners...... to act on the reports and the National Board of Health to commuicate the learning nationally. The act protects health care providers from sanctions as a result of reporting. In January 2004, the Act on Patient Safety in the Danish health care system was put into force. In the first twelve months 5740...... adverse events were reported. the reports were analyzed locally (hospital and region), anonymized ad then sent to the National Board af Health. The Act on Patient Safety has driven the work with patient safety forward but there is room for improvement. Continuous and improved feedback from all parts...
Scott, W; Chilcot, J; Guildford, B; Daly-Eichenhardt, A; McCracken, L M
Acceptance and Commitment Therapy (ACT) has growing support for chronic pain. However, more accessible treatment delivery is needed. This study evaluated the feasibility of online ACT for patients with complex chronic pain in the United Kingdom to determine whether a larger trial is justified. Participants with chronic pain and clinically meaningful disability and distress were randomly assigned to ACT online plus specialty medical pain management, or specialty medical management alone. Participants completed questionnaires at baseline, and 3- and 9-month post-randomization. Primary feasibility outcomes included recruitment, retention and treatment completion rates. Secondary outcomes were between-groups effects on treatment outcomes and psychological flexibility. Of 139 potential participants, 63 were eligible and randomized (45% recruitment rate). Retention rates were 76-78% for follow-up assessments. Sixty-one per cent of ACT online participants completed treatment. ACT online was less often completed by employed (44%) compared to unemployed (80%) participants. Fifty-six per cent of ACT online participants rated themselves as 'much improved' or better on a global impression of change rating, compared to only 20 per cent of control participants. Three-month effects favouring ACT online were small for functioning, medication and healthcare use, committed action and decentring, medium for mood, and large for acceptance. Small-to-medium effects were maintained for functioning, healthcare use and committed action at 9 months. Online ACT for patients with chronic pain in the United Kingdom appears feasible to study in a larger efficacy trial. Some adjustments to treatment and trial procedures are warranted, particularly to enhance engagement among employed participants. This study supports the feasibility of online Acceptance and Commitment Therapy for chronic pain in the United Kingdom and a larger efficacy trial. Refinements to treatment delivery, particularly to
Parker, Melissa J; de Laat, Sonya; Schwartz, Lisa
Prospective informed consent is required for most research involving human participants; however, this is impracticable under some circumstances. The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS) outlines the requirements for research involving human participants in Canada. The need for an exception to consent (deferred consent) is recognised and endorsed in the TCPS for research in individual medical emergencies; however, little is known about substitute decision-maker (SDM) experiences. A paediatric resuscitation trial (SQUEEZE) (NCT01973907) using an exception to consent process began enrolling at McMaster Children's Hospital in January 2014. This qualitative research study aims to generate new knowledge on SDM experiences with the exception to consent process as implemented in a randomised controlled trial. The SDMs of children enrolled into the SQUEEZE pilot trial will be the sampling frame from which ethics study participants will be derived. Qualitative research study involving individual interviews and grounded theory methodology. SDMs for children enrolled into the SQUEEZE pilot trial. Up to 25 SDMs. Qualitative methodology: SDMs will be invited to participate in the qualitative ethics study. Interviews with consenting SDMs will be conducted in person or by telephone, taped and professionally transcribed. Participants will be encouraged to elaborate on their experience of being asked to consent after the fact and how this process occurred. Data gathering and analysis will be undertaken simultaneously. The investigators will collaborate in developing the coding scheme, and data will be coded using NVivo. Emerging themes will be identified. This research represents a rare opportunity to interview parents/guardians of critically ill children enrolled into a resuscitation trial without their knowledge or prior consent. Findings will inform implementation of the exception to consent process in the planned definitive SQUEEZE
Silberberg, A; Murray, P; Christensen, J; Asano, T
Humans chose 10 times between two roulette wheels projected on a monitor. During the first trial, the left wheel provided a hypothetical $100 with p = .94, and the right wheel provided $250 with p = .39. A titration procedure adjusted the probability of a $250 win across trials to permit estimation of an indifference point between alternatives. In Experiment 1, intertrial-interval duration (25 vs. 90 s) and whether sessions began with an intertrial interval or a trial were varied in a 2 x 2 design in this risky-choice procedure. Risk aversion (preference for the $100 wheel) increased with intertrial interval but was unaffected by whether sessions began with a trial or an intertrial interval. In Experiment 2, all sessions began with a trial, and subjects were informed that the experiment ended after 10 trials. Intertrial-interval duration had no effect on choice. In Experiment 3, intertrial-interval duration and whether subjects were given $10 or $10,000 before beginning were varied among four groups in a 2 x 2 design. In all other ways, the procedure was unchanged from Experiment 2. Intertrial interval had no effect on choice, but the $10,000 groups showed less risk aversion than the $10 groups. These results can be explained more readily in terms of Kahneman and Tversky's (1984) notion of "framing of the prospect" than in terms of Rachlin, Logue, Gibbon, and Frankel's (1986) behavioral account of risky choice.
Poole-Wilson, Philip A.; Kirwan, Bridget-Anne; Voko, Zoltan; de Brouwer, Sophie; Dunselman, Peter H. J. M.; van Dalen, Frederik J.; Lubsen, Jacobus
Background and Objective: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. Methods: Data from a trial comparing long-acting nifedipine
Luchtenberg, Malou; Maeckelberghe, Els; Locock, Louise; Powell, Lesley; Verhagen, A. A. Eduard
Given the lack of knowledge about safety and efficacy of many treatments for children, pediatric clinical trials are important, but recruitment for pediatric research is difficult. Little is known about children's perspective on participating in trials. The purpose of this study was to understand
Koziol-McLain, Jane; McLean, Christine; Rohan, Maheswaran; Sisk, Rose; Dobbs, Terry; Nada-Raja, Shyamala; Wilson, Denise; Vandal, Alain C
Automated eHealth Web-based research trials offer people an accessible, confidential opportunity to engage in research that matters to them. eHealth trials may be particularly useful for sensitive issues when seeking health care may be accompanied by shame and mistrust. Yet little is known about people's early engagement with eHealth trials, from recruitment to preintervention autoregistration processes. A recent randomized controlled trial that tested the effectiveness of an eHealth safety decision aid for New Zealand women in the general population who experienced intimate partner violence (isafe) provided the opportunity to examine recruitment and preintervention participant engagement with a fully automated Web-based registration process. The trial aimed to recruit 340 women within 24 months. The objective of our study was to examine participant preintervention engagement and recruitment efficiency for the isafe trial, and to analyze dropout through the registration pathway, from recruitment to eligibility screening and consent, to completion of baseline measures. In this case study, data collection sources included the trial recruitment log, Google Analytics reports, registration and program metadata, and costs. Analysis included a qualitative narrative of the recruitment experience and descriptive statistics of preintervention participant engagement and dropout rates. A Koyck model investigated the relationship between Web-based online marketing website advertisements (ads) and participant accrual. The isafe trial was launched on September 17, 2012. Placement of ads in an online classified advertising platform increased the average number of recruited participants per month from 2 to 25. Over the 23-month recruitment period, the registration website recorded 4176 unique visitors. Among 1003 women meeting eligibility criteria, 51.55% (517) consented to participate; among the 501 women who enrolled (consented, validated, and randomized), 412 (82.2%) were
informed consent (58%, cumbersome procedures (58%, difficulty in long-term follow up (33%, and insufficient tools for explanation and obtaining informed consent (8%. Conclusion This survey showed that successful physician recruiters consider a support system with CRC of value, and that they are skillful in obtaining informed consent. These views and attitudes may have originated from past experience involving clinical trials. In this regard, we need to develop an infrastructure to enlighten physicians on this support system for the promotion of clinical trials.
McLean, Christine; Rohan, Maheswaran; Sisk, Rose; Dobbs, Terry; Nada-Raja, Shyamala; Wilson, Denise; Vandal, Alain C
Background Automated eHealth Web-based research trials offer people an accessible, confidential opportunity to engage in research that matters to them. eHealth trials may be particularly useful for sensitive issues when seeking health care may be accompanied by shame and mistrust. Yet little is known about people’s early engagement with eHealth trials, from recruitment to preintervention autoregistration processes. A recent randomized controlled trial that tested the effectiveness of an eHealth safety decision aid for New Zealand women in the general population who experienced intimate partner violence (isafe) provided the opportunity to examine recruitment and preintervention participant engagement with a fully automated Web-based registration process. The trial aimed to recruit 340 women within 24 months. Objective The objective of our study was to examine participant preintervention engagement and recruitment efficiency for the isafe trial, and to analyze dropout through the registration pathway, from recruitment to eligibility screening and consent, to completion of baseline measures. Methods In this case study, data collection sources included the trial recruitment log, Google Analytics reports, registration and program metadata, and costs. Analysis included a qualitative narrative of the recruitment experience and descriptive statistics of preintervention participant engagement and dropout rates. A Koyck model investigated the relationship between Web-based online marketing website advertisements (ads) and participant accrual. Results The isafe trial was launched on September 17, 2012. Placement of ads in an online classified advertising platform increased the average number of recruited participants per month from 2 to 25. Over the 23-month recruitment period, the registration website recorded 4176 unique visitors. Among 1003 women meeting eligibility criteria, 51.55% (517) consented to participate; among the 501 women who enrolled (consented, validated
Beatrice de Graaf
Full Text Available On 24 August 2012, the judges of the Oslo District Court passed their final verdict in the case of Anders Behring Breivik, declaring Breivik criminally sane and legally responsible for the killing of 77 people during the bombing of government buildings in Oslo and the shooting spree on the island of Utøya on 22 July 2011. This Research Paper examines to what extent the Breivik trial attained the goals of criminal justice: retribution, prevention, restoring democratic order and upholding the rule of law. Furthermore, it aims to determine if the trial contributed to the need for closure in society. The Research Paper concludes that the trial did indeed have a positive impact on the coping mechanisms in Norwegian society and that most Norwegians viewed the trial as a positive counter-weight to the brutality of Breivik’s acts. Overall, the trial was viewed as an example of justice and as a trial that upheld the democratic values of Norwegian society – in stark contrast to Breivik’s values.
Hanna, Mina; Minga, Albert; Fao, Paulin; Borand, Laurence; Diouf, Assane; Mben, Jean-Marc; Gad, Rita R; Anglaret, Xavier; Bazin, Brigitte; Chene, Geneviève
consideration, that is, in the case of vulnerable participants (children, pregnant women). Proposed indicators are the result of expert consensus and reflect their experience in the HIV field. Relevance to existing trials and extrapolation to other fields must be assessed. This innovative program allowed ANRS sites located in RLCs to share their GCP implementation experiences in order to build a list of relevant indicators for clinical trials. The next step is to collect data from ongoing HIV and hepatitis C trials in these settings and will assess the relevance of these indicators to document current quality of performance among trials in resource-limited settings.
Burke, Holly M; Packer, Catherine A; Spector, Hannah L; Hubacher, David
Increased use of long-acting reversible contraception (LARC) can reduce unintended pregnancies. However, significant barriers exist to LARC uptake, particularly high up-front costs. In North Carolina in 2014, we interviewed 34 purposively-selected participants (aged 20-30 years) enrolled in a partially randomized patient preference trial to learn about their experiences with and attitudes toward contraception in this unique trial context. Cost of LARC was important in participants' decision-making. Experiencing an unintended pregnancy motivated women to switch to LARC. No participants who tried LARC, even those who experienced side effects, regretted it. Several participants regretted discontinuing their LARC. Concerns about insertion and removal did not influence future willingness to try LARC. Participants discussed the importance of affordability and feeling in control when choosing a contraceptive method. Cost, combined with uncertainty over whether LARC is the right method for them, may deter young women from trying LARC. Intrauterine devices and implants should be made affordable so that women can try them without significant financial commitment. Affordability will likely increase uptake, which will reduce unintended pregnancies. Regret from discontinuing LARC was more more frequently reported than regret from trying LARC. Providers should offer young women LARC and counsel to support continuation.
Rapport, Frances; Clement, Clare
BackgroundQualitative research methods are increasingly used within trials to address broader research questions than quantitative methods can address alone. Qualitative methods enable health professionals, service users and other stakeholders to contribute their views and experiences when evaluating health care treatments, interventions or policies. They can influence trial design, allowing for a fuller engagement with research questions, aims and objectives and clarify the complexities of p...
Fox, John A.; Olson, Dennis G.
The potential market for irradiated chicken breasts was investigated using a mail survey and a retail trial. Results from the mail survey suggested a significantly higher level of acceptability of irradiated chicken than did the retail trial. A subsequent market experiment involving actual purchases showed levels of acceptability similar to that of the mail survey when similar information about food irradiation was provided
Full Text Available Abstract Background HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania. Methods A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs conducted immediately after their 4, 24 and 52 week follow-up visits. Results 99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews. In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy. Conclusions
Farmer Andrew J
align it with their clinical practices and experiences. Conclusions To understand trial findings, foster attainment of endpoints, and promote protocol fidelity, it may be necessary to look beyond individual patient characteristics and experiences. Specifically, the context of trial delivery, the impact of staff involvement, and the difficulties staff may encounter in balancing competing 'clinical' and 'research' roles and responsibilities may need to be considered and addressed.
Tanja-Dijkstra, Karin; Pahl, Sabine; White, Mathew P; Andrade, Jackie; May, Jon; Stone, Robert J; Bruce, Malcolm; Mills, Ian; Auvray, Melissa; Gabe, Rhys; Moles, David R
Dental anxiety and anxiety-related avoidance of dental care create significant problems for patients and the dental profession. Distraction interventions are used in daily medical practice to help patients cope with unpleasant procedures. There is evidence that exposure to natural scenery is beneficial for patients and that the use of virtual reality (VR) distraction is more effective than other distraction interventions, such as watching television. The main aim of this randomized controlled trial is to determine whether the use of VR during dental treatment can improve the overall dental experience and recollections of treatment for patients, breaking the negative cycle of memories of anxiety leading to further anxiety, and avoidance of future dental appointments. Additionally, the aim is to test whether VR benefits dental patients with all levels of dental anxiety or whether it could be especially beneficial for patients suffering from higher levels of dental anxiety. The third aim is to test whether the content of the VR distraction can make a difference for its effectiveness by comparing two types of virtual environments, a natural environment and an urban environment. The effectiveness of VR distraction will be examined in patients 18 years or older who are scheduled to undergo dental treatment for fillings and/or extractions, with a maximum length of 30 minutes. Patients will be randomly allocated into one of three groups. The first group will be exposed to a VR of a natural environment. The second group will be exposed to a VR of an urban environment. A third group consists of patients who receive standard care (control group). Primary outcomes relate to patients' memories of the dental treatment one week after treatment: (a) remembered pain, (b) intrusive thoughts and (c) vividness of memories. Other measures of interest are the dental experience, the treatment experience and the VR experience. Current Controlled Trials ISRCTN41442806.
...); prior experience completing pre-purchase counseling or education; regular access to a computer and... New Privacy Act System of Records, Pre-Purchase Homeownership Counseling Demonstration and Impact... of record is the Pre-Purchase Homeownership Counseling Demonstration and Impact Evaluation Random...
... period of disability but not to disability insurance benefits, and you are not entitled to any other type of disability benefit under title II of the Social Security Act (i.e., child's benefits based on... disability benefits (see paragraph (e) of this section). (e) When the trial work period begins and ends. The...
Full Text Available Abstract Background Alcohol dependence is a significant and costly problem in the UK yet only 6% of people a year receive treatment. Current service provision based on the treatment of acute episodes of illness and emphasising personal choice and motivation results in a small proportion of these patients engaging with alcohol treatment. There is a need for interventions targeted at the population of alcohol dependent patients who are hard to engage in conventional treatment. Assertive Community Treatment (ACT, a model of care based on assertive outreach, has been used for treating patients with severe mental illnesses and presents a promising avenue for engaging patients with primary alcohol dependence. So far there has been little research on this. Methods/Design In this single blind exploratory randomised controlled trial, a total of 90 alcohol dependent participants will be recruited from community addiction services. After completing a baseline assessment, they will be assigned to one of two conditions: (1 ACT plus care as usual, or (2 care as usual. Those allocated to the ACT plus care as usual will receive the same treatment that is routinely provided by services, plus a trained key worker who will provide ACT. ACT comprises intensive and assertive contact at least once a week, over 50% of contacts in the participant's home or local community, and comprehensive case management across social and health care, for a period of one year. All participants will be followed up at 6 months and 12 months to assess outcome post randomisation. The primary outcome measures will be alcohol consumption: mean drinks per drinking day and percentage of days abstinent measured by the Time Line Follow Back interview. Secondary outcome measures will include severity of alcohol dependence, alcohol related problems, motivation to change, social network involvement, quality of life, therapeutic relationship and service use. Other outcome variables are treatment
Moshabela, Mosa; Zuma, Thembelihle; Orne-Gliemann, Joanna; Iwuji, Collins; Larmarange, Joseph; McGrath, Nuala
The ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomized trial in rural South Africa uses a "test and treat" approach. Home-based testing services and antiretroviral treatment initiation satellite clinics were implemented in every cluster as part of the trial. A social science research agenda was nested within TasP with the aim of understanding the social, economic and contextual factors that affect individuals, households, communities and health systems with respect to TasP. Considering the rural nature of the trial setting, we sought to understand community perceptions and experiences of the TasP Trial interventions as seen through the eyes of traditional health practitioners (THPs). A qualitative study design was adopted using four repeat focus group discussions conducted with nine THPs, combined with community walks and photo-voice techniques, over a period of 18 months. A descriptive, interpretive and explanatory approach to analysis was adopted. Findings indicate that THPs engaged with the home-based testing services and HIV clinics established for TasP. Specifically, home-based testing services were perceived as relatively successful in increasing access to HIV testing. A major gap observed by THPs was linkage to HIV clinics. Most of their clients, and some of the THPs themselves, found it difficult to use HIV clinics due to fear of labelling, stigma and discrimination, and the ensuing personal implications of unsolicited disclosure. On the one hand, a growing number of patients diagnosed with HIV have found sanctuary with THPs as alternatives to clinics. On the other hand, THPs in turn have been struggling to channel patients suspected of HIV into clinics through referrals. Therefore, acceptability of the TasP test and treat approach by THPs is a major boost to the intervention, but further success can be achieved through strengthened ties with communities to combat stigma and effectively link patients into HIV care, including partnerships with THPs
Full Text Available The elevated plus-maze (EPM test is one of the most commonly used behavioural assays to evaluate anxiety-related behaviour in rodents. It is a rather economic test which usually uses a short (5 min protocol and does not require conditioning of the animals. The critical measure for anxiety is the time spent in the open arms of the maze. A confounding problem of the EPM is the so called one-trial tolerance (OTT, characterised by a marked decrease of open arm exploration in spite of treatment with anxiolytic acting benzodiazepines upon re-exposure to the EPM. This consistent finding is often raised as an evidence for the inappropriateness to re-test rodents in the EPM. However, a reliable re-test paradigm would broaden the usability and effectiveness of this test.Therefore, we tested how a prolongation of the inter-trial interval to 28 days (instead of the usual 24 hours, and an additional change of the testing room would affect the open arm time and other behaviours on the EPM. In two experiments, drug naive Wistar rats were exposed to the EPM on trial 1, and treated intraperitoneally with either vehicle or midazolam (0.25 mg/kg 30 min before trial 2. Then, trial 2 (28 days after trial 1 was carried out in either the same testing room (Exp. 1 or a second unfamiliar room (Exp. 2.Twenty-eight days after trial 1 the open arm time of the rats in the vehicle treated control rats of both experimental groups was comparable to that of the first trial, independent of the testing room. Most importantly, we found that the treatment with the benzodiazepine midazolam had a significantly anxiolytic-like (i.e. increase of open arm time effect in trial 2 only when conducted in the previously unfamiliar testing room (Exp. 2. We suggest that in order to reliably re-test the EPM and to prevent confounding effects due to the OTT, an inter-trial interval of 28 days and a change in testing rooms reinstates anxiolytic-like actions of benzodiazepines
Rodbard, Helena W.; Tripathy, Devjit; Vidrio Velázquez, Maricela; Demissie, Marek; Tamer, Søren C.; Piletič, Milivoj
Aim To confirm glycaemic control superiority of mealtime fast‐acting insulin aspart (faster aspart) in a basal–bolus (BB) regimen vs basal‐only insulin. Materials and methods In this open‐label, randomized, 18‐week trial (51 sites; 6 countries), adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c] ± SD: 7.9% ± 0.7% [63.1 ± 7.5 mmol/mol]) receiving basal insulin and oral antidiabetic drugs underwent 8‐week optimization of prior once‐daily ba...
The problem of evil has vexed philosophers and theologians for centuries and anthropologists, sociologists, psychoanalysts and analytical psychologists in more recent times. Numerous theories have been proposed but there is still little agreement on such basic questions as the nature of evil, what constitutes and motivates an evil act, and how we resolve conflicts between individuals and groups in which evil acts are being committed. I am proposing that evil should be used as an adjective, and not as a noun. As such it should be employed to qualify acts of persons rather than their character. This change would enable us to eschew foundational explanations of evil and, therefore, to examine evil acts in their contexts and so better discern their nature and motivation. I will contend that evil acts begin when an individual makes, or members of a group make, assertions about the 'naturalness' of their own acts and, correspondingly, the 'unnaturalness' of the acts of others. I will suggest that this results from the anxiety that ensues when they cannot adequately signify their experience of these acts. When this occurs, those so treated are dispossessed of their 'personhood', allowing members of the 'natural' group to violate their 'boundaries' with impunity. These violations can range from the relatively innocuous such as being ignored to the extreme such as genocide. I am asserting that all these acts should be termed evil as they derive from the same semiotic process of 'naturalizaton'. I will discuss ways of preventing individuals or groups from embarking on the process of 'naturalization' and describe the types of contexts that might reduce or eliminate the commission of evil acts by those already engaged in their perpetration. To demonstrate these ideas I will use examples from my personal experience, from analytic theory and from the 'troubles' in Northern Ireland.
Aranda, Fernando; Buqué, Aitziber; Bloy, Norma; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo
One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications. PMID:26451319
... 25 Indians 2 2010-04-01 2010-04-01 false Act (The Act). 700.33 Section 700.33 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.33 Act (The Act). (a) The Act. The Act is Pub. L. 93-531, (88 Stat...
This paper will describe the impact of the Act on mental health care service delivery in ... basic principles of community psychiatry as well as .... allocation, mental health policy, quality assurance and ... Community psychiatry: An audit of the.
The present investigation deals with the implementation of open-loop up-link power control using a beacon signal in the down-link frequency band as the control parameter. A power control system was developed and tested using the ACTS satellite. ACTS carries beacon signals in both up- and down-link bands with which the relationship between the up- and down-link fading can be established. A power controlled carrier was transmitted to the ACTS satellite from a NASA operated ground station and the transponded signal was received at COMSAT Laboratories using a terminal that was routinely used to monitor the two ACTS beacon signals. The experiment ran for a period of approximately six months and the collected data were used to evaluate the performance of the power control system. A brief review of propagation factors involved in estimating the up-link fade using a beacon signal in the down-link band are presented. The power controller design and the experiment configuration are discussed. Results of the experiment are discussed.
Tarr, Robert; Hsu, Dan; Kulcsar, Zsolt; Bonvin, Christophe; Rufenacht, Daniel; Alfke, Karsten; Stingele, Robert; Jansen, Olav; Frei, Donald; Bellon, Richard; Madison, Michael; Struffert, Tobias; Dorfler, Arnd; Grunwald, Iris Q; Reith, Wolfgang; Haass, Anton
The purpose of this study was to assess the initial post-market experience of the device and how it is compared with the Penumbra Pivotal trial used to support the 510k application. A retrospective case review of 157 consecutive patients treated with the Penumbra system at seven international centers was performed. Primary endpoints were revascularization of the target vessel (TIMI score of 2 or 3), good functional outcome as defined by a modified Rankin scale (mRS) score of ≤2 and incidence of procedural serious adverse events. Results were compared with those of the Penumbra pivotal trial. A total of 157 vessels were treated. Mean baseline values at enrollment were: age 65 years, NIHSS score 16. After use of the Penumbra system, 87% of the treated vessels were revascularized to TIMI 2 (54%) or 3 (33%) as compared with 82% reported in the Pivotal trial. Nine procedural serious adverse events were reported in 157 patients (5.7%). All-cause mortality was 20% (32/157), and 41% had a mRS of ≤2 at 90-day follow-up as compared with only 25% in the Pivotal trial. Patients who were successfully revascularized by the Penumbra system had significantly better outcomes than those who were not. Initial post-market experience of the Penumbra system revealed that the revascularization rate and safety profile of the device are comparable to those reported in the Pivotal trial. However, the proportion of patients who had good functional outcome was higher than expected.
Henderson, Gail E; Peay, Holly L; Kroon, Eugene; Cadigan, Rosemary Jean; Meagher, Karen; Jupimai, Thidarat; Gilbertson, Adam; Fisher, Jill; Ormsby, Nuchanart Q; Chomchey, Nitiya; Phanuphak, Nittaya; Ananworanich, Jintanat; Rennie, Stuart
Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption (ATI), involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through a longitudinal decision-making study nested in a Thai acute HIV research cohort. In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks. These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach. PMID:29127137
Three trial sections using two warm-mix asphalt (WMA) technologies were constructed in various locations in Virginia in 2006, and experiences with these trial sections were used in the development of the Virginia Department of Transportation's specia...
Full Text Available In the empirical part of the following paper, professional service is shown in the context of a biographical experience of a professional—a family law attorney. In terms of method, this undertaking is precarious. Its sense lies in gaining an understanding of the biographically and historically motivated potentials and limits of professional services. A differentiated look at professional services is facilitated when you know the stories out of which specific procedures have resulted. In overcoming the crude classification of "professionalized," "not professionalized," and "de-professionalized," it is possible to further differentiate theories of professionalization (Talcott PARSONS, Ulrich OEVERMANN, Fritz SCHÜTZE. Up until now detailed examinations are missing of the genesis of concrete professional acting, even though the topic has been worked out clearly, especially in studies of teachers' work. URN: urn:nbn:de:0114-fqs0801537
Gunawardena, Nalika; Kurotani, Kayo; Indrawansa, Susantha; Nonaka, Daisuke; Mizoue, Tetsuya; Samarasinghe, Diyanath
School health promotion has been shown to improve the lifestyle of students, but it remains unclear whether school-based programs can influence family health. We developed an innovative program that enables school children to act as change agents in promoting healthy lifestyles of their mothers. The objective of this study was to examine the effect of the child-initiated intervention on weight, physical activity and dietary habit of their mothers. A 12-month cluster randomized trial was conducted, with school as a cluster. Participants were mothers with grade 8 students, aged around 13 years, of 20 schools in Homagama, Sri Lanka. Students of the intervention group were trained by facilitators to acquire the ability to assess noncommunicable disease risk factors in their homes and take action to address them, whereas those of the comparison group received no intervention. Body weight, step count and lifestyle of their mothers were assessed at baseline and post-intervention. Multi-level multivariable linear regression and logistic regression were used to assess the effects of intervention on continuous and binary outcomes, respectively. Of 308 study participants, 261 completed the final assessment at 12 month. There was a significantly greater decrease of weight and increase of physical activity in the intervention group. The mean (95% confidence interval) difference comparing the intervention group with the control group was -2.49 (-3.38 to -1.60) kg for weight and -0.99 (-1.40 to -0.58) kg/m(2) for body mass index. The intervention group had a 3.25 (95% confidence interval 1.87-5.62) times higher odds of engaging in adequate physical activity than the control group, and the former showed a greater number of steps than the latter after intervention. The intervention group showed a greater reduction of household purchase of biscuits and ice cream. A program to motivate students to act as change agents of family's lifestyle was effective in decreasing weight and
The purpose of this analysis was to examine the effect of long-acting beta(2)-adrenoceptor agonists (LABAs) on the asthma exacerbation rate in pediatric patients. Randomized controlled trials (RCT) that included the use of LABAs to treat symptoms of pediatric asthma in children on inhaled cortico...
Calder, Allyson; Nunnerley, Jo; Mulligan, Hilda; Ahmad Ali, Nordawama; Kensington, Gemma; McVicar, Tim; van Schaik, Olivia
For individuals with spinal cord injury the long term benefits of physical activity are well documented, however the majority of this population report inactivity secondary to participatory barriers. Research investigating physically intensive exercise programs for people with spinal cord injury is limited, with even less attention paid to the experience of the participants. To explore the experiences of persons with spinal cord injury of their participation in the New Zealand arm of the Spinal Cord Injury and Physical Activity (SCIPA) 'Full-On' randomized controlled trial. Eight participants recruited to SCIPA Full-On completed individual virtual video diary interviews three times across the duration of their twelve week Full-On trial. Expectations and highs and lows of the program were recorded via a webcam. The video diary data were transcribed verbatim and analyzed inductively for themes. Three independent themes were identified from the data: the participants' excitement of opportunity to participate in SCIPA Full-On' randomized controlled trial, personal rewards from participation and also the frustrations to participation they experienced. This study provides valuable information on factors that motivate participation in physical activity for individuals with spinal cord injury, within a research setting. The findings highlighted the importance of accessibility and a supportive network which may be a way to provide individuals with spinal cord injury the means to become self-efficacious to participate in community physical activity outside of the research environment. Copyright © 2017 Elsevier Inc. All rights reserved.
Golshan, Nasser (Editor)
The NASA Propagation Experimenters (NAPEX) meeting is convened each year to discuss studies supported by the NASA Propagation Program. Representatives from the satellite communications industry, academia and government who have an interest in space-ground radio wave propagation are invited to NAPEX meetings for discussions and exchange of information. The reports delivered at this meeting by program managers and investigators present recent activities and future plans. This forum provides an opportunity for peer discussion of work in progress, timely dissemination of propagation results, and close interaction with the satellite communications industry. NAPEX XXI took place in El Segundo, California on June 11-12, 1997 and consisted of three sessions. Session 1, entitled "ACTS Propagation Study Results & Outcome " covered the results of 20 station-years of Ka-band radio-wave propagation experiments. Session 11, 'Ka-band Propagation Studies and Models,' provided the latest developments in modeling, and analysis of experimental results about radio wave propagation phenomena for design of Ka-band satellite communications systems. Session 111, 'Propagation Research Topics,' covered a diverse range of propagation topics of interest to the space community, including overviews of handbooks and databases on radio wave propagation. The ACTS Propagation Studies miniworkshop was held on June 13, 1997 and consisted of a technical session in the morning and a plenary session in the afternoon. The morning session covered updates on the status of the ACTS Project & Propagation Program, engineering support for ACTS Propagation Terminals, and the Data Center. The plenary session made specific recommendations for the future direction of the program.
Weis, Erik; Hölzl, Rainer; Breuer, Dirk; Lange, Christoph
This paper reports on a FTTH field trial with GPON (Gigabit-capable passive optical network) technology in the network of Deutsche Telekom in the region of the cities of Berlin and Potsdam. Focus of this trial was to gain practical experience regarding GPON technology, fibre installation in existing ducts with micro duct technology, fibre cabling in customer buildings and impact on operational processes. Furthermore it is reported on an initial Deutsche Telekom FTTB deployment based on GPON technology in the city of Dresden with the main targets to obtain practical deployment and operation experiences with fibre-based access networks and to provide broadband access to a part of the city formerly not servable by DSL (digital subscriber line) technology.
Chipps, Bradley E; Lanier, Bob; Milgrom, Henry; Deschildre, Antoine; Hedlin, Gunilla; Szefler, Stanley J; Kattan, Meyer; Kianifard, Farid; Ortiz, Benjamin; Haselkorn, Tmirah; Iqbal, Ahmar; Rosén, Karin; Trzaskoma, Benjamin; Busse, William W
Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma (AA) that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications. Since its initial licensing for use in adults and adolescents 12 years of age and older, the clinical efficacy, safety, and tolerability of omalizumab have been demonstrated in several published clinical trials in children aged 6 to less than 12 years with moderate-to-severe AA. These studies supported the approval of the pediatric indication (use in children aged ≥6 years) by the European Medicines Agency in 2009 and the US Food and Drug Administration in 2016. After this most recent change in licensing, we review the outcomes from clinical trials in children with persistent AA receiving omalizumab therapy and observational studies from the past 7 years of clinical experience in Europe. Data sources were identified by using PubMed in 2016. Guidelines and management recommendations and materials from the recent US Food and Drug Administration's Pediatric Advisory Committee meeting are also reviewed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Acosta, Roberto J.; Lagin, Alan R.; Larko, Jeffrey M.; Narvaez, Adabelle
One of the most important aspects of a satellite communication system design is the accurate estimation of antenna performance degradation. Pointing error, end coverage gain, peak gain degradation, etc. are the main concerns. The thermal or dynamic distortions of a reflector antenna structural system can affect the far-field antenna power distribution in a least four ways. (1) The antenna gain is reduced; (2) the main lobe of the antenna can be mispointed thus shifting the destination of the delivered power away from the desired locations; (3) the main lobe of the antenna pattern can be broadened, thus spreading the RF power over a larger area than desired; and (4) the antenna pattern sidelobes can increase, thus increasing the chances of interference among adjacent beams of multiple beam antenna system or with antenna beams of other satellites. The in-house developed NASA Lewis Research Center thermal/structural/RF analysis program was designed to accurately simulate the ACTS in-orbit thermal environment and predict the RF antenna performance. The program combines well establish computer programs (TRASYS, SINDA and NASTAN) with a dual reflector-physical optics RF analysis program. The ACTS multibeam antenna configuration is analyzed and several thermal cases are presented and compared with measurements (pre-flight).
Ali, Myzoon; Ashburn, Ann; Bowen, Audrey; Brodie, Eric; Corr, Susan; Drummond, Avril; Edmans, Judi; Gladman, John; Kalra, Lalit; Langhorne, Peter; Lees, Kennedy R; Lincoln, Nadina; Logan, Pip; Mead, Gillian; Patchick, Emma; Pollock, Alex; Pomeroy, Val; Sackley, Catherine; Sunnerhagen, Katherina S; van Vliet, Paulette; Walker, Marion; Brady, Marian
Stroke rehabilitation is a complex intervention. Many factors influence the interaction between the patient and the elements of the intervention. Rehabilitation interventions are aimed at altering different domains of patient outcome including body functions, activity and participation. As a consequence, randomised clinical trials in this area are difficult to design. We developed an archive of stroke rehabilitation trials (VISTA-Rehab) to act as a resource to help trialists model and design future rehabilitation studies. We developed specific eligibility criteria for the entry of stroke rehabilitation trials into the archive. We established a Steering Committee to oversee projects and publications and commenced the recruitment of rehabilitation trials into this resource. As of August 2009, VISTA-Rehab contains data from 23 stroke rehabilitation trials (>3400 patients). Demographic data, including age [median=73, interquartile range (63,79)], gender (male=53%) and initial dependency [median baseline Barthel index score=6, interquartile range (9,19)], are available for all patients. Outcome measures include the modified Rankin Scale, Barthel Index, Rivermead Motor Assessment, Fugl-Meyer Assessment, General Health Questionnaire and Nottingham Extended Activities of Daily Living Scale. VISTA-Rehab expands the Virtual International Stroke Trials Archive to include rehabilitation trials. Anonymised data can be used to examine questions specific to stroke rehabilitation and to generate novel hypotheses. © 2010 The Authors. International Journal of Stroke © 2010 World Stroke Organization.
Baumann, R.; Faber, P.
At the mixed-oxide (MOX) processing facility formerly operated by ALKEM GmbH in Hanau, Germany - which was taken over to Siemens in 1988 and renamed Siemens' Hanau Fuel Fabrication Plant, MOX facility - around 8500 kg of plutonium were processed to make MOX fuel rods and fuel assemblies since production started in 1965. After shutdown of the facility by the authorities in mid-1991 for political reasons, the remaining nuclear fuel materials were processed during the subsequent ''cleanout'' phase starting in 1997 into rods and assemblies suitable for long-term storage. The last step in cleanout consisted of ''flushing'' the production equipment with depleted uranium and thoroughly cleaning the gloveboxes. During cleanout around 700 kg of plutonium were processed in the form of mixed oxides. The cleanout phase including the subsequent cleaning and flushing operations ended on schedule in September 2001 without any significant problems. Starting in mid-1999, the various glovebox dismantling techniques were tested using uncontaminated components while cleanout was still in progress and then, once these trials had been successfully completed, further qualified through use on actual components. The pilot-phase trials required four separate licenses under Section 7, Subsection (3) of the German Atomic Energy Act. Thanks to detailed advance planning and experience from the pilot trials the individual dismantling steps could be described in sufficient detail for the highly complex German licensing procedure. The first partial license for decommissioning the MOX facility under Sec. 7, Subsec. (3) of the Atomic Energy Act was issued on May 28, 2001. It mainly covers dismantling of the interior equipment inside the gloveboxes a well as the gloveboxes themselves. Actual decommissioning work inside the former production areas of the MOX facility started on a large scale in early September 2001. (orig.)
Helverschou, Sissel Berge; Steindal, Kari; Nøttestad, Jim Aage; Howlin, Patricia
The processes of arrest, investigation, trial and imprisonment are often extremely difficult for individuals with autism spectrum disorders. In this study, nine offenders with autism spectrum disorders were interviewed about the circumstance surrounding the criminal acts, their views of the arrest, the police interrogation, the trial and the…
Pettersen, Gunn; Rosenvinge, Jan H; Bakland, Maria; Wynn, Rolf; Mathisen, Therese Fostervold; Sundgot-Borgen, Jorunn
Women with bulimia nervosa and binge eating disorder often suffer for many years before they seek professional help. Evidence-based treatments like cognitive-behavioural therapy (CBT) might be poorly accessible, and about 50% of those who receive CBT respond to it. Such outcome may reflect the heterogeneous nature of eating disorders, and addressing this heterogeneity calls for expanding the portfolio of treatment options. In particular, it is important to explore such options' acceptability, tolerability and affordability expressed through experiences with the treatment. This protocol outlines the rationale and design of a qualitative study. It captures experiences from patients and therapists who were involved in a randomised controlled trial (RCT) exploring the efficacy of a new group-based treatment programme combining physical exercise and dietary therapy. 15 patients with bulimia nervosa or binge eating disorder, 10 therapists (physical trainers and dietitians) and 6-10 patients who dropped out of the RCT will be semistructurally interviewed. All interviews will be analysed using a systematic text condensation approach. Results will be presented in peer-reviewed international journals, and at relevant international conferences. Key findings will be available to study participants as well as to patient organisations and health authorities. The overall study meets the intent and requirements of the Health Research Act and the Declaration of Helsinki. It is approved by the regional committee for medical research ethics (2013/1871). NCT02079935; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Full Text Available BACKGROUND: Guided internet-delivered cognitive behavior therapy (ICBT has been tested in several trials on social anxiety disorder (SAD with moderate to large effects. The aims of this study were threefold. First, to compare the effects of ICBT including online discussion forum with a moderated online discussion forum only. Second, to investigate if knowledge about SAD increased following treatment and third to compare the effects of inexperienced versus experienced therapists on patient outcomes. METHODS: A total of 204 participants with a primary diagnosis of SAD were included and randomized to either guided ICBT or the control condition. ICBT consisted of a 9-week treatment program which was guided by either psychology students at MSc level (n = 6 or by licensed psychologists with previous experience of ICBT (n = 7. A knowledge test dealing with social anxiety was administered before and after treatment. Measures of social anxiety and secondary outcomes dealing with general anxiety, depression, and quality of life were administered before and after treatment. In addition, a 1-year follow-up was conducted on the treated individuals. RESULTS: Immediately following treatment, the ICBT group showed superior outcome on the Liebowitz Social Anxiety Scale self-report version with a between group posttreatment Hedges g effect size of g = 0.75. In addition, significant differences on all the secondary outcomes were observed. Gains were well maintained one year later. Knowledge, as assessed by the knowledge test, increased following treatment with little gain in the control group. Therapist experience did not result in different outcomes, but experienced therapists logged in less frequently compared to the inexperienced therapists, suggesting that they needed less time to support patients. DISCUSSION: We conclude that guided ICBT reduce symptoms of SAD, increase knowledge about SAD and that therapist experience does not make a difference
Style, Sarah; Beard, B James; Harris-Fry, Helen; Sengupta, Aman; Jha, Sonali; Shrestha, Bhim P; Rai, Anjana; Paudel, Vikas; Thondoo, Meelan; Pulkki-Brannstrom, Anni-Maria; Skordis-Worrall, Jolene; Manandhar, Dharma S; Costello, Anthony; Saville, Naomi M
The increasing availability and capabilities of mobile phones make them a feasible means of data collection. Electronic Data Capture (EDC) systems have been used widely for public health monitoring and surveillance activities, but documentation of their use in complicated research studies requiring multiple systems is limited. This paper shares our experiences of designing and implementing a complex multi-component EDC system for a community-based four-armed cluster-Randomised Controlled Trial in the rural plains of Nepal, to help other researchers planning to use EDC for complex studies in low-income settings. We designed and implemented three interrelated mobile phone data collection systems to enrol and follow-up pregnant women (trial participants), and to support the implementation of trial interventions (women's groups, food and cash transfers). 720 field staff used basic phones to send simple coded text messages, 539 women's group facilitators used Android smartphones with Open Data Kit Collect, and 112 Interviewers, Coordinators and Supervisors used smartphones with CommCare. Barcoded photo ID cards encoded with participant information were generated for each enrolled woman. Automated systems were developed to download, recode and merge data for nearly real-time access by researchers. The systems were successfully rolled out and used by 1371 staff. A total of 25,089 pregnant women were enrolled, and 17,839 follow-up forms completed. Women's group facilitators recorded 5717 women's groups and the distribution of 14,647 food and 13,482 cash transfers. Using EDC sped up data collection and processing, although time needed for programming and set-up delayed the study inception. EDC using three interlinked mobile data management systems (FrontlineSMS, ODK and CommCare) was a feasible and effective method of data capture in a complex large-scale trial in the plains of Nepal. Despite challenges including prolonged set-up times, the systems met multiple data
Ahola Kohut, Sara; Stinson, Jennifer; Forgeron, Paula; Luca, Stephanie; Harris, Lauren
To explore the perceived benefits and challenges of acting as a young adult peer mentor to adolescents with chronic illness. A qualitative descriptive study, using interviews and a focus group, explored the perceptions of young adult peer mentors following participation in the iPeer2Peer program, a Skype-based peer-mentorship program for adolescents with chronic illness. Interviews and focus group data were transcribed and analyzed using inductive content analysis. Ten peer mentors (20.00 ± 1.49 years old, range 17-22 years; diagnosed with chronic pain [n = 4] or juvenile idiopathic arthritis [n = 6]) who mentored four mentees (±2.55 mentees, range = 1-10 mentees) participated. Four main categories were identified: social connection, personal growth, mentor role in mentee growth, and logistics of mentorship. Acting as a peer mentor online is a feasible and rewarding experience that supports the mentor's own illness self-management, social connection, and personal growth. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: email@example.com
Hamlet, Claire; Williamson, Heidi; Harcourt, Diana
Qualitative research methods embedded within feasibility trials are of significant value as they can provide important information for a definitive trial, often unable to be fulfilled by quantitative methods alone. In addition, such information can aid researchers running other trials or evaluating interventions on a similar topic. Aim This study aimed to explore GP and nurses' experiences of recruiting to a trial exploring the feasibility of evaluating YP Face IT, a novel online psychosocial intervention to support young people with appearance-altering conditions. During the recruitment period, a focus group with participating GPs and nurses explored recruitment challenges. In addition, at the end of the recruitment period, telephone interviews were conducted with eight GPs and nurses involved in recruiting to the study, in order to inform a definitive trial of YP Face IT. Transcripts were subjected to thematic analysis. Findings Despite reporting that the study was valuable and interesting, interviewees struggled to recruit in-consultation. They appeared to lack confidence in raising the sensitive issue of a visible difference and adopted strategies to avoid mentioning the topic. Participants felt the nature of the target population, as well as pressures of the primary care environment presented challenges to recruitment, but welcomed YP Face IT as an intervention that could address unmet support needs. Primary care staff may benefit from training to help them raise the subject of a visible difference with young people in order to identify those that require additional support.
Full Text Available Identifying sources of the apparent variability in non-stationary scenarios is a fundamental problem in many biological data analysis settings. For instance, neurophysiological responses to the same task often vary from each repetition of the same experiment (trial to the next. The origin and functional role of this observed variability is one of the fundamental questions in neuroscience. The nature of such trial-to-trial dynamics however remains largely elusive to current data analysis approaches. A range of strategies have been proposed in modalities such as electro-encephalography but gaining a fundamental insight into latent sources of trial-to-trial variability in neural recordings is still a major challenge. In this paper, we present a proof-of-concept study to the analysis of trial-to-trial variability dynamics founded on non-autonomous dynamical systems. At this initial stage, we evaluate the capacity of a simple statistic based on the behaviour of trajectories in classification settings, the trajectory coherence, in order to identify trial-to-trial dynamics. First, we derive the conditions leading to observable changes in datasets generated by a compact dynamical system (the Duffing equation. This canonical system plays the role of a ubiquitous model of non-stationary supervised classification problems. Second, we estimate the coherence of class-trajectories in empirically reconstructed space of system states. We show how this analysis can discern variations attributable to non-autonomous deterministic processes from stochastic fluctuations. The analyses are benchmarked using simulated and two different real datasets which have been shown to exhibit attractor dynamics. As an illustrative example, we focused on the analysis of the rat's frontal cortex ensemble dynamics during a decision-making task. Results suggest that, in line with recent hypotheses, rather than internal noise, it is the deterministic trend which most likely underlies
Woods, Adam J; Cohen, Ronald; Marsiske, Michael; Alexander, Gene E; Czaja, Sara J; Wu, Samuel
Adults over age 65 represent the fastest growing population in the US. Decline in cognitive abilities is a hallmark of advanced age and is associated with loss of independence and dementia risk. There is a pressing need to develop effective interventions for slowing or reversing the cognitive aging process. While certain forms of cognitive training have shown promise in this area, effects only sometimes transfer to neuropsychological tests within or outside the trained domain. This paper describes a NIA-funded Phase III adaptive multisite randomized clinical trial, examining whether transcranial direct current stimulation (tDCS) of frontal cortices enhances neurocognitive outcomes achieved from cognitive training in older adults experiencing age-related cognitive decline: the Augmenting Cognitive Training in Older Adults study (ACT). ACT will enroll 360 participants aged 65 to 89 with age-related cognitive decline, but not dementia. Participants will undergo cognitive training intervention or education training-control combined with tDCS or sham tDCS control. Cognitive training employs a suite of eight adaptive training tasks focused on attention/speed of processing and working memory from Posit Science BrainHQ. Training control involves exposure to educational nature/history videos and related content questions of the same interval/duration as the cognitive training. Participants are assessed at baseline, after training (12weeks), and 12-month follow-up on our primary outcome measure, NIH Toolbox Fluid Cognition Composite Score, as well as a comprehensive neurocognitive, functional, clinical and multimodal neuroimaging battery. The findings from this study have the potential to significantly enhance efforts to ameliorate cognitive aging and slow dementia. Copyright © 2017 Elsevier Inc. All rights reserved.
The operating experience feedback system of VINCOTTE, called ARIANE, consists, among others, of preparing synthesis reports on specific safety concerns. A recent report deals with significant events caused by extranous acts. Events attributable to human error are numerous. Confusion errors have already been analysed in several publications (NES IRS 664 etc.). However, are described here some ten incidents where extranous acts occurred: ZION 2 (September 76), OYSTER CREEK (May 79), PALISADES (January 81), CATAWBA (August 85), etc. The contributing factors for these unfortunate initiatives are explained; several resort to psychological influences. Corrective actions are discussed, and some general lessons are drawn. (author)
Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd
Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737
Gil-Extremera, B; Jiménez-López, P; Mediavilla-García, J D
Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Chhoa, C. Y.; Sawyer, A.; Ayers, S.; Pushpa-Rajah, A.; Duley, L.
BACKGROUND: The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. Preterm birth can be rapid and unexpected, allowing little time for the usual consent process. Therefore, in addition to the usual procedure for written consent, a two-stage pathway for consent for use when birth was imminent was developed. The aims of this study were to explore clinicians’ views and experiences of offering two consent pathways for recruit...
Chhoa, Celine Y.; Sawyer, Alexandra; Ayers, Susan; Pushpa-Rajah, Angela; Duley, Lelia
Background The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. Preterm birth can be rapid and unexpected, allowing little time for the usual consent process. Therefore, in addition to the usual procedure for written consent, a two-stage pathway for consent for use when birth was imminent was developed. The aims of this study were to explore clinicians? views and experiences of offering two consent pathways for recruitment...
Full Text Available Abstract Background Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal. These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability. Methods In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively or placebo (NCT#00590577. Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE rates and relative risks (RR with 95% confidence intervals (CI versus placebo were determined. Results Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS mean PANSS total score at Day 8 (p = 0.037. After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo and Day 36 (p Conclusions Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1 compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose
Sarah V Kedenge
Full Text Available There is considerable interest in the potential of private sector subsidies to increase availability and affordability of artemisinin-based combination therapies (ACTs for malaria treatment. A cluster randomized trial of such subsidies was conducted in 3 districts in Kenya, comprising provision of subsidized packs of paediatric ACT to retail outlets, training of retail staff, and community awareness activities. The results demonstrated a substantial increase in ACT availability and coverage, though patient counselling and adherence were suboptimal. We conducted a qualitative study in order to understand why these successes and limitations occurred.Eighteen focus group discussions were conducted, 9 with retailers and 9 with caregivers, to document experiences with the intervention. Respondents were positive about intervention components, praising the focused retailer training, affordable pricing, strong promotional activities, dispensing job aids, and consumer friendly packaging, which are likely to have contributed to the positive access and coverage outcomes observed. However, many retailers still did not stock ACT, due to insufficient supplies, lack of capital and staff turnover. Advice to caregivers was poor due to insufficient time, and poor recall of instructions. Adherence by caregivers to dosing guidelines was sub-optimal, because of a wish to save tablets for other episodes, doses being required at night, stopping treatment when the child felt better, and the number and bitter taste of the tablets. Caregivers used a number of strategies to obtain paediatric ACT for older age groups.This study has highlighted that important components of a successful ACT subsidy intervention are regular retailer training, affordable pricing, a reliable supply chain and community mobilization emphasizing patient adherence and when to seek further care.
Kedenge, Sarah V; Kangwana, Beth P; Waweru, Evelyn W; Nyandigisi, Andrew J; Pandit, Jayesh; Brooker, Simon J; Snow, Robert W; Goodman, Catherine A
There is considerable interest in the potential of private sector subsidies to increase availability and affordability of artemisinin-based combination therapies (ACTs) for malaria treatment. A cluster randomized trial of such subsidies was conducted in 3 districts in Kenya, comprising provision of subsidized packs of paediatric ACT to retail outlets, training of retail staff, and community awareness activities. The results demonstrated a substantial increase in ACT availability and coverage, though patient counselling and adherence were suboptimal. We conducted a qualitative study in order to understand why these successes and limitations occurred. Eighteen focus group discussions were conducted, 9 with retailers and 9 with caregivers, to document experiences with the intervention. Respondents were positive about intervention components, praising the focused retailer training, affordable pricing, strong promotional activities, dispensing job aids, and consumer friendly packaging, which are likely to have contributed to the positive access and coverage outcomes observed. However, many retailers still did not stock ACT, due to insufficient supplies, lack of capital and staff turnover. Advice to caregivers was poor due to insufficient time, and poor recall of instructions. Adherence by caregivers to dosing guidelines was sub-optimal, because of a wish to save tablets for other episodes, doses being required at night, stopping treatment when the child felt better, and the number and bitter taste of the tablets. Caregivers used a number of strategies to obtain paediatric ACT for older age groups. This study has highlighted that important components of a successful ACT subsidy intervention are regular retailer training, affordable pricing, a reliable supply chain and community mobilization emphasizing patient adherence and when to seek further care.
Full Text Available Abstract Background Randomised controlled clinical trials are performed to resolve uncertainty concerning comparator interventions. Appropriate acknowledgment of uncertainty enables the concurrent achievement of two goals : the acquisition of valuable scientific knowledge and an optimum treatment choice for the patient-participant. The ethical recruitment of patients requires the presence of clinical equipoise. This involves the appropriate choice of a control intervention, particularly when unapproved drugs or innovative interventions are being evaluated. Discussion We argue that the choice of a control intervention should be supported by a systematic review of the relevant literature and, where necessary, solicitation of the informed beliefs of clinical experts through formal surveys and publication of the proposed trial's protocol. Summary When clinical equipoise is present, physicians may confidently propose trial enrollment to their eligible patients as an act of therapeutic beneficence.
Douglas H. Marin dos Santos; Álvaro N. Atallah
The relationship between clinical research and the pharmaceutical industry has placed clinical trials in jeopardy. According to the medical literature, more than 70% of clinical trials are industry-funded. Many of these trials remain unpublished or have methodological flaws that distort their results. In 2007, it was signed into law the Food and Drug Administration Amendments Act (FDAAA), aiming to provide publicly access to a broad range of biomedical information to be made available on the ...
Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena
After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.
Lawman, Hannah G; Wilson, Dawn K; Van Horn, M Lee; Zarrett, Nicole
Previous research has shown that social contextual factors are important in understanding physical activity (PA) behavior, although little is known about how these factors may relate to PA, especially in underserved adolescents (low income, minorities). This study examined how motivation may differentially mediate the relationship of two social contextual variables (i.e., peer and parent social support) and moderate-to-vigorous PA (MVPA). Baseline data (n = 1421 sixth graders, 54% female, 72% African American) from the Active by Choice Today (ACT) trial in underserved adolescents were analyzed. Motivation was examined as a mediator of the relationships between peer social support, parent social support, and MVPA (measured by 7-day accelerometer estimates). Motivation and peer but not parent support were significantly related to MVPA overall. Significant mediation effects were found indicating motivation partially mediated the relation between peer social support and MVPA and to a lesser degree parent support and MVPA. These findings provide support for the importance of social contextual influences, especially peer social support, on underserved adolescents' PA and motivation for PA.
Maruani, Annabel; Boutron, Isabelle; Baron, Gabriel; Ravaud, Philippe
To evaluate the impact of sending an email to responsible parties of completed trials that do not comply with the Food and Drug Administration Amendments Act 801 legislation, to remind them of the legal requirement to post results. Cohort embedded pragmatic randomized controlled trial. Trials registered on ClinicalTrials.gov. 190 out of 379 trials randomly selected by computer generated randomization list to receive the intervention (personalized emails structured as a survey and sent by one of us to responsible parties of the trials, indirectly reminding them of the legal requirement and potential penalties for non-compliance). The primary outcome was the proportion of results posted on ClinicalTrials.gov at three months. The secondary outcome was the proportion posted at six months. In a second step, two assessors blinded to the intervention group collected the date of the first results being received on ClinicalTrials.gov. A post hoc sensitivity analysis excluding trials wrongly included was performed. Among 379 trials included, 190 were randomized to receive the email intervention. The rate of posting of results did not differ at three months between trials with or without the intervention: 36/190 (19%) v 24/189 (13%), respectively (relative risk 1.5, 95% confidence interval 0.9 to 2.4, P=0.096) but did at six months: 46/190 (24%) v 27/189 (14%), 1.7, 1.1 to 2.6, P=0.014. In the sensitivity analysis, which excluded 48/379 trials (13%), 26/190 (14%) and 22/189 (12%), respectively, results were significant at three months (relative risk 5.1, 1.1 to 22.9, P=0.02) and at six months (4.1, 1.3 to 10.6, P=0.001). Sending email reminders about the FDA's legal requirement to post results at ClinicalTrials.gov improved significantly the posting rate at six months but not at three months.Trial registration ClinicalTrials.gov NCT01658254. © Maruani et al 2014.
Nugent, Timothy; Upton, David; Cimpoesu, Mihai
The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using a blockchain to prove the existence of documents describing pre-specified endpoints in clinical trials. Here, we extend the idea by using smart contracts - code, and data, that resides at a specific address in a blockchain, and whose execution is cryptographically validated by the network - to demonstrate how trust in clinical trials can be enforced and data manipulation eliminated. We show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history. PMID:28357041
Nugent, Timothy; Upton, David; Cimpoesu, Mihai
The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using a blockchain to prove the existence of documents describing pre-specified endpoints in clinical trials. Here, we extend the idea by using smart contracts - code, and data, that resides at a specific address in a blockchain, and whose execution is cryptographically validated by the network - to demonstrate how trust in clinical trials can be enforced and data manipulation eliminated. We show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history.
Aziz, V M
This study aims at identifying any local trend in the appeal process and to determine if we are complying with the MHA 1983 and the Code of Practice by reviewing all the appeals to Mental Health Review Tribunals in a psychiatric hospital in South Wales for the period from 2004 to 2008. The total numbers of sections and appeals remain steady over the years. Men are slightly more detained than women mainly under Sections 2 and 3 of the MH Act 1983. The main diagnoses for detention were: bipolar affective disorder, schizophrenia and psychosis. 95% of cases had appeals and 5% referrals. A hearing was held in 52% of cases (n=60), the RMO discharged 38% of patients and the patient withdrew appeal in 10% of cases. 95% of cases were British White ethnicity. Single men tended to appeal more than women 68% vs. 32%. There was no observed trend in the result of the appeals and the proportions of appeal discharged by the hearing remained unchanged. The results of the appeals were not associated with gender, ethnicity, marital status, age or the type of section involved. The patients who were previously detained tend to appeal more, i.e. the more number of detentions, the more number of appeals. In only 12% of cases who had the hearings, the appeal was successful and the patients were discharged from their sections. The study shows steady volume of sections and appeals and the appeals are no more likely to result in discharge. The amendments of the Act 2007 also attract an increase in the appeal process especially in relation to the Community Treatment Orders and the Deprivation of Liberty. The use of both the Act and the Mental Capacity Act 2005 will increase workload for all involved practitioners. 2009 Elsevier Ltd and Faculty of Forensic and Legal Medicine.
Background Qualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design. Methods Health services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP). Results The qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component. Conclusions We recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials. PMID:23433341
ATCk restricts its jurisdiction by imposing some doctrines such as minimum contact, forum non-convenience, political question, International commuty and act of state doc trine. Besides that, it also ignores the International criminal law principles such as presumption of innocence, expeditious trial, equity ofarms and the atendance ofthe suspect in the court. The existence of par im parem in habet Imperium principle recognized ininternational law causes the decision of American Courtis meanin...
This paper explores the connection of offshoring and outsourcing to nonconsensual global pharmaceutical trials in low-income countries. After discussing reasons why the topic of nonconsensual offshored clinical trials may be overlooked in bioethics literature, I suggest that when pharmaceutical corporations offshore clinical trials today, nonconsensual experiments are often foreseeable and not simply the result of aberrant ethical conduct by a few individuals. Offshoring of clinical trials is structured so that experiments can be presented as health care in a unique form of outsourcing from the host country to pharmaceutical corporations. Bioethicists' assessments of the risks and potential benefits of offshore corporate pharmaceutical trials should therefore systematically include not only the hoped for benefits and the risks of the experimental drug but also the risk that subjects will not have consented, as well as the broader international consequences of nonconsensual experimentation.
Full Text Available Since airflow obstruction in chronic obstructive pulmonary disease (COPD is to some extent reversible, bronchodilators play an important role in the maintenance treatment of COPD the more they reduce hyperinflation and, as a result, improve dyspnoea and exercise capacity. Since parasympathetic activity is the dominant reversible component of airflow obstruction in COPD, inhaled short-acting anticholinergic agents (SAAC, in particular ipratropium, became an efficient and safe first-line treatment, especially when combined with a short-acting beta2-adrenergic receptor agonist. Even better results were obtained when combining the SAAC ipratropium to a long-acting beta2-adrenergic receptor agonist (LABA, once they became available. Recently, tiotropium bromide, the first of a new class of selective and long-acting anticholinergic agents was introduced for once-daily maintenance treatment of COPD patients. Several large long-term randomised clinical trials comparing tiotropium to placebo as well as to the SAAC ipratropium and the LABA salmeterol, have confirmed the long-acting and superior bronchodilator effect of tiotropium without any evidence of drug tolerance developing. These studies also have clearly demonstrated that tiotropium positively affects several other important health outcomes, such as dyspnoea sensation, exercise capacity, utilisation of rescue bronchodilators, health-related quality of life, COPD exacerbations and hospitalisations because of exacerbations. The improvement in these real-life outcomes appears related to the reduction in both static and dynamic hyperinflation. In all these studies, tiotropium was well tolerated and safe; the only relevant side-effect encountered being dry mouth, usually mild and often transitory. Finally, it has been shown that the combination of tiotropium with a LABA affords superior bronchodilatation than both agents alone, indicating that both classes of long-acting bronchodilators should be
Pharmacological treatment of chronic obstructive pulmonary disease (COPD) relies principally on long-acting bronchodilators. Inhaled corticosteroids (ICS) were introduced for COPD two decades ago, despite the fact that no randomized trial had yet assessed their efficacy for this indication. Since then, the numerous randomized trials and meta-analyses performed to justify their use in COPD have been contradictory and controversial. Moreover, observational studies have reported efficacy rates so exceptional that they are almost too good to be true. These studies contain important methodological flaws that produce the appearance of efficacy. The randomized trials infringe the fundamental principle of intention-to-treat analysis, an analysis necessary to prevent important biases. Two other complications are the interruption of treatment at the moment of randomization and the use of a run-in period; in both cases, the withdrawal of treatment can introduce bias. The observational studies reporting phenomenal reductions in mortality with ICS were distorted by "immortal time" bias. Finally, recent data suggest that the effect of ICS/bronchodilator combinations is due mainly to the effect of the long-acting bronchodilator. Given the absence of proof of the efficacy of inhaled corticosteroids in COPD and their associated risks, especially of ocular damage and pneumonia, and particularly among the elderly, as well as the high doses currently prescribed in COPD, it is difficult to recommend their use in this indication. They should be prescribed in COPD for at most a limited population of patients.
Burns, Bridgit; Grindlay, Kate; Dennis, Amanda
Long-acting reversible contraception (LARC) and sterilization are popular contraceptive methods. However, they have been associated with safety concerns and coercive practices. We aimed to understand women's opinions and experiences related to these methods, including whether the methods' fraught histories influence use or interest. Between May and July 2013, we conducted an online survey with a convenience sample of 520 women aged 14 to 45. We used quota sampling to ensure women of color were at least 60% of our sample. Descriptive statistics, χ(2) tests, and multivariable logistic regression were used to estimate participants' awareness of, interest in, and experiences with LARCs and sterilization. Overall, 30% of women reported current LARC use and 67% interest in future LARC use. Four percent reported sterilization use and 48% interest in future sterilization. In multivariate analyses, current LARC use was lower among Asian women versus White women (odds ratio [OR], 0.24), and interest in future use was higher among women aged 14 to 24 versus 35 to 45 (OR, 5.49). Interest in sterilization was higher among women aged 14 to 24 and 25 to 34 versus 35 to 45 (ORs, 3.29-3.66) and women with disabilities (OR, 1.64), and lower among Black compared with White women (OR, 0.41). Method misperceptions were evident, and concerns about contraceptive coercion were reported. Concerns about contraceptive coercion were not predominant reasons for noninterest in LARCs and sterilization, but were reported by some participants. Lower sterilization interest among Black women and higher sterilization interest among women with disabilities warrant further research. Efforts to address misperceptions about LARCs and sterilization, including their safety and efficacy, are needed. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.
Act 588 of the Republic of Ghana entitled, Atomic Energy Commission Act, 2000, amends and consolidates the Atomic Energy Commission Act, 204 of 1963 relating to the establishment of the Atomic Energy Commission. Act 588 makes provision for the Ghana Atomic Energy Commission to establish more institutes for the purpose of research in furtherance of its functions and also promote the commercialization of its research and development results. (E.A.A.)
Pistorius, A. G.; van de Wijgert, J. H. H. M.; Sebola, M.; Friedland, B.; Nagel, E.; Bokaba, C.; Hoosen, A. A.
The Microbicide Division of the Department of Medical Microbiology at MEDUNSA, South Africa, recently completed a phase II expanded safety trial of the candidate microbicide Carraguard. A microbicide is a vaginal product that women might use, if proven safe and effective, to protect themselves from
Most neuroscience cognitive experiments involve repeated presentations of various stimuli across several minutes or a few hours. It has been observed that brain responses, even to the same stimulus, evolve over the course of the experiment. These changes in brain activation and connectivity are believed to be associated with learning and/or habituation. In this paper, we present two general approaches to modeling dynamic brain connectivity using electroencephalograms (EEGs) recorded across replicated trials in an experiment. The first approach is the Markovian regime-switching vector autoregressive model (MS-VAR) which treats EEGs as realizations of an underlying brain process that switches between different states both within a trial and across trials in the entire experiment. The second is the slowly evolutionary locally stationary process (SEv-LSP) which characterizes the observed EEGs as a mixture of oscillatory activities at various frequency bands. The SEv-LSP model captures the dynamic nature of the amplitudes of the band-oscillations and cross-correlations between them. The MS-VAR model is able to capture abrupt changes in the dynamics while the SEv-LSP directly gives interpretable results. Moreover, it is nonparametric and hence does not suffer from model misspecification. For both of these models, time-evolving connectivity metrics in the frequency domain are derived from the model parameters for both functional and effective connectivity. We illustrate these two models for estimating cross-trial connectivity in selective attention using EEG data from an oddball paradigm auditory experiment where the goal is to characterize the evolution of brain responses to target stimuli and to standard tones presented randomly throughout the entire experiment. The results suggest dynamic changes in connectivity patterns over trials with inter-subject variability.
Full Text Available Betty Tai, Steven Sparenborg, Udi E Ghitza, David Liu Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA Abstract: The Patient Protection and Affordable Care Act (2010 and the Mental Health Parity and Addiction Equity Act (2008 expand substance use disorder (SUD care services in the USA into general medical settings. Care offered in these settings will engage substance-using patients in an integrated and patient-centered environment that addresses physical and mental health comorbidities and follows a chronic care model. This expansion of SUD services presents a great need for evidence-based practices useful in general medical settings, and reveals several research gaps to be addressed. The National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse can serve an important role in this endeavor. High-priority research gaps are highlighted in this commentary. A discussion follows on how the National Drug Abuse Treatment Clinical Trials Network can transform to address changing patterns in SUD care to efficiently generate evidence to guide SUD treatment practice within the context of recent US health care legislation. Keywords: Patient Protection and Affordable Care Act, National Drug Abuse Treatment Clinical Trials Network, substance use disorders, practice-based research network, electronic health records
Dam, C. van; Vliet, P.J. van; Schuurman, K.; Maltha, S.R.; Leyten, A.J.M.; Dirks, M.W.S.
The main objective of the ACTS MEDIAN project is to build a high speed WCPN/LAN demonstrator system for multimedia applications and demonstrate it in user trials. The demonstrator system, consisting of one base station and two portable stations, is capable of handling high speed (up to 150 Mbit/s)
Dogra, Anjali P; Dorman, Todd
To provide an overview of key elements of the Affordable Care Act. To evaluate ways in which the Affordable Care Act will likely impact the practice of critical care medicine. To describe strategies that may help health systems and providers effectively adapt to changes brought about by the Affordable Care Act. Data sources for this concise review include search results from the PubMed and Embase databases, as well as sources relevant to public policy such as the text of the Patient Protection and Affordable Care Act and reports of the Congressional Budget Office. As all of the Affordable Care Act's provisions will not be fully implemented until 2019, we also drew upon cost, population, and utilization projections, as well as the experience of existing state-based healthcare reforms. The Affordable Care Act represents the furthest reaching regulatory changes in the U.S. healthcare system since the 1965 Medicare and Medicaid provisions of the Social Security Act. The Affordable Care Act aims to expand health insurance coverage to millions of Americans and place an emphasis on quality and cost-effectiveness of care. From models which link pay and performance to those which center on episodic care, the Affordable Care Act outlines sweeping changes to health systems, reimbursement structures, and the delivery of critical care. Staffing models that include daily rounding by an intensivist, palliative care integration, and expansion of the role of telemedicine in areas where intensivists are inaccessible are potential strategies that may improve quality and profitability of ICU care in the post-Affordable Care Act era.
Gilfoyle, David; Mortensen, Eva; Christoffersen, Eva Dam; Leff, Jonathan A; Beckert, Michael
TransCon growth hormone (GH) is a sustained-release inactive prodrug consisting of unmodified GH transiently bound to an inert carrier molecule designed to release fully active GH over a one-week period. This was a first-in-man phase 1 randomized trial was to evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of TransCon GH as compared to equivalent doses of daily GH (Omnitrope) or placebo in healthy adults. Forty-four healthy male adults were randomized to 4 cohorts of 11 subjects, distributed in a 7:2:2 ratio (TransCon GH: Omnitrope: placebo). A single injection of 4 possible TransCon GH doses (i.e., 0.04, 0.08, 0.16, or 0.24mg GH/kg/wk) or two different Omnitrope doses (i.e., 0.08 or 0.16mg GH/kg/wk divided into 7 equal daily doses) were administered with subjects evaluated for adverse events, immunogenicity, and GH and insulin-like growth factor-1 (IGF-1) levels. TransCon GH was well tolerated; no serious adverse events occurred, no injection site reaction differences between TransCon GH, Omnitrope, or placebo were identified, no nodules or lipoatrophy were reported, and no anti-GH binding antibodies or ECG changes were detected. Overall, the exposure of GH (C max ) and IGF-1 (AUC 0-168h ) following administration of equivalent doses of TransCon GH and Omnitrope were similar. GH and IGF-1 kinetics showed a dose-proportional increase following a single SC administration of TransCon GH and indicated that the prodrug is suitable for weekly administration. These results support advancement of TransCon GH to pediatric and adult GHD trials. Clinical trial registration numbers: NCT01010425 (clinicaltrials.gov). Copyright © 2017 Elsevier Ltd. All rights reserved.
Ridgeway, Jennifer L; Asiedu, Gladys B; Carroll, Katherine; Tenney, Meaghan; Jatoi, Aminah; Radecki Breitkopf, Carmen
Clinical trials are vital in the context of ovarian cancer and may offer further treatment options during disease recurrence, yet enrollment remains low. Understanding patient and family member experiences with identifying trials can inform engagement and education efforts. Interviews were conducted with 33 patients who had experience with clinical trial conversations and 39 nominated family members. Thematic analysis examined experiences and generated findings for clinical practice. Trial conversations with providers at diagnosis were uncommon and often overwhelming. Most participants delayed engagement until later in the disease course. With hindsight, though, some wished they considered trials earlier. Difficulty identifying appropriate trials led some to defer searching to providers, but then they worried about missed opportunities. Most family members felt unqualified to search. Trial conversations during clinical encounters should start early and include specifying search responsibilities of providers, patients, and family. Patients and family members can be engaged in searches but need guidance. Trials should be discussed throughout the disease course, even if patients are not ready to participate or are not making a treatment decision. Education should focus on identifying trials that meet search criteria. Transparency regarding each individual's role in identifying trials is critical. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
I have come to the conclusion that for high school physics classroom and laboratory experiences, simpler is better! In this paper I describe a very simple and effective lab experience that my AP students have thoroughly enjoyed year after year. I call this lab exercise "Time Trials." The experiment is simple in design and it is a lot of fun for…
Okonta, Patrick I
The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria.
Chhoa, Celine Y; Sawyer, Alexandra; Ayers, Susan; Pushpa-Rajah, Angela; Duley, Lelia
The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. Preterm birth can be rapid and unexpected, allowing little time for the usual consent process. Therefore, in addition to the usual procedure for written consent, a two-stage pathway for consent for use when birth was imminent was developed. The aims of this study were to explore clinicians' views and experiences of offering two consent pathways for recruitment to a randomised trial of timing of cord clamping at very preterm birth. This was a qualitative study using semi-structured interviews. Clinicians from eight hospitals in the UK who had been involved in offering consent to the Cord Pilot Trial were invited to take part in an interview. Clinicians were interviewed in person or by telephone. Interviews were analysed using inductive systematic thematic analysis. Seventeen clinicians who had either offered usual written consent only (n = 6) or both the two-stage pathway (with oral assent before the birth and written consent after the birth) and usual written consent (n = 11) were interviewed. Six themes were identified: (1) team approach to offering participation; (2) consent form as a record; (3) consent and participation as a continual process; (4) different consent pathways for different trials; (5) balance between time, information, and understanding; and (6) validity of consent. Overall, clinicians were supportive of the two-stage consent pathway. Some clinicians felt that in time-critical situations oral assent presented an advantage over the usual written consent as they provided information on a "need to know" basis. However, there was some concern about how much information should be given for oral assent, and how this is understood by women when birth is imminent. The two-stage pathway for consent developed for use in the Cord Pilot Trial when birth was imminent was acceptable to clinicians for comparable low-risk studies
Horita, Nobuyuki; Goto, Atsushi; Shibata, Yuji; Ota, Erika; Nakashima, Kentaro; Nagai, Kenjiro; Kaneko, Takeshi
Three classes of inhaler medications are used to manage chronic obstructive pulmonary disease (COPD): long-acting beta-agonists (LABA), long-acting muscarinic antagonists (LAMA), and inhaled corticosteroids (ICS). When two classes of medications are required, LAMA plus LABA (LAMA+LABA) and LABA plus ICS (LABA+ICS) are often selected because these combinations can be administered via a single medication device. The previous Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidance recommended LABA+ICS as the first-line treatment for managing stable COPD in high-risk people of categories C and D. However, the updated GOLD 2017 guidance recommends LAMA+LABA over LABA+ICS. To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD. We performed an electronic search of the Cochrane Airways Group Specialised Register (2 February 2016), ClinicalTrials.gov (4 June 2016), and the World Health Organization Clinical Trials Search Portal (4 June 2016), followed by a handsearch (5 June 2016). Two review authors screened and scrutinised the selected articles. We included individual randomised controlled trials, parallel-group trials, and cross-over trials comparing LAMA+LABA and LABA+ICS for stable COPD. The minimum accepted trial duration was one month and trials should have been conducted in an outpatient setting. Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (OR), and continuous data as mean differences (MD), with 95% confidence interval (CI) using Review Manager 5. Exacerbations were measured by counting the number of people experiencing one or more exacerbation. We included 11 studies comprising 9839 participants in our quantitative analysis. Most studies included people with moderate to severe COPD, without recent exacerbations. One pharmaceutical sponsored trial that included only people with
The purpose of this article is to compile the destruction of GMO trials from academic or governmental research institutes in Europe, in a factual manner and to highlight their main characteristics. About 80 acts of vandalism against academic or governmental research on GMOs are identified, mainly in 4 countries; namely France, Germany, the United Kingdom and Switzerland. Examples are also provided for Italy and Belgium. The general conclusions that can be drawn from these acts are also discussed.
Teaching Speech Acts
Full Text Available In this paper I argue that pragmatic ability must become part of what we teach in the classroom if we are to realize the goals of communicative competence for our students. I review the research on pragmatics, especially those articles that point to the effectiveness of teaching pragmatics in an explicit manner, and those that posit methods for teaching. I also note two areas of scholarship that address classroom needs—the use of authentic data and appropriate assessment tools. The essay concludes with a summary of my own experience teaching speech acts in an advanced-level Portuguese class.
..., to obtain a permit under the Resource Conservation and Recovery Act (``RCRA'') for its ownership and... emissions from the TMW at the facility; perform trial and risk burns for the TMW to identify appropriate incinerator level and risk based operating and control parameters for the unit; file a notification and...
The African Development of AIDS Prevention Trials (ADAPT2) capacity building initiative is an African-Canadian partnership that aims to increase the number and quality of HIV prevention trials led by African researchers. Building on experience gained during ADAPT1 - funded by the Global Health Research Initiative ...
The African Development of AIDS Prevention Trials (ADAPT2) capacity building initiative is an African-Canadian partnership that aims to increase the number and quality of HIV prevention trials led by African researchers. Building on experience gained during ADAPT1 - funded by the Global Health Research Initiative ...
Tsunemoto, H.; Arai, T.; Morita, S.; Ishikawa, T.; Aoki, Y.; Takada, N.; Kamata, S.
Between November, 1975 and November, 1981, 825 patients were treated with 30 MeV (d-Be) neutrons at the National Institute of Radiological Sciences, Chiba. At the Institute of Medical Science, Tokyo, 302 patients were referred to the Radiation Therapy department and were treated with 16 MeV (d-Be) neutrons. The emphasis of these clinical trials with fast neutrons was placed on the estimation of the effect of fast neutrons for locally advanced cancers or radioresistant cancers, and on evaluation of the rate of complication of normal tissues following irradiation with fast neutrons. Results were evaluated for patients with previously untreated cancer; local control of the tumor was observed in 59.1%. Complications requiring medical care developed in only 32 patients. Late reaction of soft tissue seemed to be more severe than that observed with photon beams. The results also suggest that for carcinoma of the larynx, esophagus, uterine cervix, Pancoast's tumor of the lung and osteosarcoma, fast neutrons were considered to be effectively applied in this randomized clinical trial. For carcinoma of the larynx, a fast neutron boost was effectively delivered, although an interstitial implant was necessarily combined with fast neutrons for carcinoma of the tongue. The cumulative survival rate of the patients with carcinoma of the esophagus treated with fast neutrons of 26% compared to the survival rate of 10.5% obtained using photons. The results also indicate that local control and relief of the symptom related to Pancoast's tumor of the lung seemed to be better with neutrons than with photons. For patients suffering from osteosarcoma, the surgical procedures preserving the function of the leg and arm were studied according to the better local control rate of the tumor following fast neutron beam therapy
Henderson, Gail E; Peay, Holly L; Kroon, Eugene; Cadigan, Rosemary Jean; Meagher, Karen; Jupimai, Thidarat; Gilbertson, Adam; Fisher, Jill; Ormsby, Nuchanart Q; Chomchey, Nitiya; Phanuphak, Nittaya; Ananworanich, Jintanat; Rennie, Stuart
Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption (ATI), involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through a longitudinal decision-making study nested in a Thai acute HIV research cohort.In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks.These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Ombao, Hernando; Fiecas, Mark; Ting, Chee-Ming; Low, Yin Fen
Most neuroscience cognitive experiments involve repeated presentations of various stimuli across several minutes or a few hours. It has been observed that brain responses, even to the same stimulus, evolve over the course of the experiment. These changes in brain activation and connectivity are believed to be associated with learning and/or habituation. In this paper, we present two general approaches to modeling dynamic brain connectivity using electroencephalograms (EEGs) recorded across replicated trials in an experiment. The first approach is the Markovian regime-switching vector autoregressive model (MS-VAR) which treats EEGs as realizations of an underlying brain process that switches between different states both within a trial and across trials in the entire experiment. The second is the slowly evolutionary locally stationary process (SEv-LSP) which characterizes the observed EEGs as a mixture of oscillatory activities at various frequency bands. The SEv-LSP model captures the dynamic nature of the amplitudes of the band-oscillations and cross-correlations between them. The MS-VAR model is able to capture abrupt changes in the dynamics while the SEv-LSP directly gives interpretable results. Moreover, it is nonparametric and hence does not suffer from model misspecification. For both of these models, time-evolving connectivity metrics in the frequency domain are derived from the model parameters for both functional and effective connectivity. We illustrate these two models for estimating cross-trial connectivity in selective attention using EEG data from an oddball paradigm auditory experiment where the goal is to characterize the evolution of brain responses to target stimuli and to standard tones presented randomly throughout the entire experiment. The results suggest dynamic changes in connectivity patterns over trials with inter-subject variability. Copyright © 2017. Published by Elsevier Inc.
specific devices, namely televisions and mobile phones. The paper focuses on the methods and discusses their benefits and the challenges associated with their application. In particular, the findings are compared to those collected through a quantitative cross-cultural survey. The experience gathered...
Saeed, Sahar; Strumpf, Erin C.; Walmsley, Sharon L.; Rollet-Kurhajec, Kathleen; Pick, Neora; Martel-Laferri?re, Valerie; Hull, Mark; Gill, M. John; Cox, Joseph; Cooper, Curtis; Klein, Marina B.
Background. ?Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have been described as revolutionary. However, it remains uncertain how effective these drugs will be for individuals coinfected with human immunodeficiency virus (HIV)?HCV. Bridging this gap between efficacy and effectiveness requires a focus on the generalizability of clinical trials. Methods. ?Generalizability of DAA trials was assessed by applying the eligibility criteria from 5 efficacy trials: NCT01479868, PHOT...
Honig, Adriaan; Kuyper, Astrid M. G.; Schene, Aart H.; van Melle, Joost P.; De Jonge, Peter; Tulner, Dorien M.; Schins, Annique; Crijns, Harry J. G. M.; Kuijpers, Petra M. J. C.; Vossen, Helen; Lousberg, Richel; Ormel, Johan
Objective: To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective
Mbonye, Anthony K.; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S.; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E.
Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. Methods A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. Findings A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 – 50·9), pshop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7– 98·4), pshop vendors using presumptive diagnosis (control arm). Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate
Esposito, Isabella; Trinks, Julieta; Soriano, Vicente
The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.
Malmstrom, Kerstin; Peszek, Iza; Al Botto; Lu, Susan; Enright, Paul L; Reiss, Theodore F
Accuracy and repeatability of spirometry measurements are essential to obtain reliable efficacy data in randomized asthma clinical trials. We report our experience with a centralized spirometry quality assurance program that we implemented in our phase III asthma trials. Six asthma trials of 4 to 21 weeks in duration were conducted at 232 clinical centers in 31 countries. Approximately 23,100 prebronchodilator and 13,700 postbronchodilator spirometry tests were collected from 2523 adult and 336 pediatric asthmatic patients. The program used a standard spirometer (the Renaissance spirometry system) with maneuver quality messages and automated quality grading of the spirometry tests. Each clinical center transmitted spirometry data weekly to a central database, where uniform monitoring of data quality was performed and feedback was provided in weekly quality reports. Seventy-nine percent of all patients performed spirometry sessions with quality that either met or exceeded American Thoracic Society standards and improved over time. Good-quality spirometry was associated with (1) less severe asthma; (2) active treatment; (3) infrequent nocturnal awakenings; (4) age above 15 years; and (5) low body weight. Maneuver-induced bronchospasm was rare. Good-quality spirometry was observed in multicenter asthma clinical trials that employed a standard spirometer and continuous monitoring. Both within- and between-patient variability decreased. Spirometry quality improved with time as study participants and technicians gained experience.
Meuwese, Julia D I; van Loon, Anouk M; Lamme, Victor A F; Fahrenfort, Johannes J
Perceptual decisions seem to be made automatically and almost instantly. Constructing a unitary subjective conscious experience takes more time. For example, when trying to avoid a collision with a car on a foggy road you brake or steer away in a reflex, before realizing you were in a near accident. This subjective aspect of object recognition has been given little attention. We used metacognition (assessed with confidence ratings) to measure subjective experience during object detection and object categorization for degraded and masked objects, while objective performance was matched. Metacognition was equal for degraded and masked objects, but categorization led to higher metacognition than did detection. This effect turned out to be driven by a difference in metacognition for correct rejection trials, which seemed to be caused by an asymmetry of the distractor stimulus: It does not contain object-related information in the detection task, whereas it does contain such information in the categorization task. Strikingly, this asymmetry selectively impacted metacognitive ability when objective performance was matched. This finding reveals a fundamental difference in how humans reflect versus act on information: When matching the amount of information required to perform two tasks at some objective level of accuracy (acting), metacognitive ability (reflecting) is still better in tasks that rely on positive evidence (categorization) than in tasks that rely more strongly on an absence of evidence (detection).
Full Text Available BACKGROUND: Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT and that fibronectin CH296 (FN-CH296 together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer. METHODS: Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up. RESULTS: Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%. CONCLUSIONS: The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies. TRIAL REGISTRATION: UMIN UMIN000001835.
Schneider, H; Stolzenburg, J-U
Since the introduction of the German Act to Combat Corruption in the Healthcare Sector concerns of fear and uncertainty are present. An elementary protection against criminal investigations can be achieved by complying with the physician professional law. Service contracts with the industry can be concluded if the interest in the service is reasonable and the payment is appropriate. There is a restrictive scale for clinical trials with already authorized products regarding any compensation granted which should correspond to the amount determined by the applicable elements of the German scale of medical fees (GOÄ). Invitations to academic training events can be accepted within an appropriate framework.
Lestariningsih; Anwar, Muhammad; Setiawan, Agus Mulyanto
The goal of this research is to investigate the act of design in discharge concept using Pendidikan Matematika Realistik Indonesia (PMRI) approach with Lapindo's Mud phenomenon as a context. Design research was chosen as the method used in this research that consists of three phases, namely preparing for the experiment, teaching experiment, and…
Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D
This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance of web-course-trained participants (intervention group) and printed-manual-trained participants (comparison group) to determine the effectiveness of the web-course in teaching CBT skills. A single DMS was needed to support all aspects of the study: web-course delivery and management, as well as randomized trial management. The authors briefly reviewed several other systems that were described as built either to handle randomized trials or to deliver and evaluate web-based training. However it was clear that these systems fell short of meeting our needs for simultaneous, coordinated management of the web-course and the randomized trial. New England Research Institute's (NERI) proprietary Advanced Data Entry and Protocol Tracking (ADEPT) system was coupled with the web-programmed course and customized for our purposes. This article highlights the requirements for a DMS that operates at the intersection of web-based course management systems and randomized clinical trial systems, and the extent to which the coupled, customized ADEPT satisfied those requirements. Recommendations are included for institutions and individuals considering conducting randomized trials and web-based training programs, and seeking a DMS that can meet similar requirements.
Riis, Jens Ove; Achenbach, Marlies; Israelsen, Poul; Kyvsgaard Hansen, Poul; Johansen, John; Deuse, Jochen
Challenged by increased globalisation and fast technological development, we carried out an experiment in the third semester of a global business engineering programme aimed at identifying conditions for training student in dealing with complex and ill-structured problems of forming a new business. As this includes a fuzzy front end, learning cannot be measured in traditional, quantitative terms; therefore, we have explored the use of reflection to convert tacit knowledge to explicit knowledge. The experiment adopted a Plan-Do-Check-Act approach and concluded with developing a plan for new learning initiatives in the subsequent year's semester. The findings conclude that (1) problem-based learning develops more competencies than ordinarily measured at the examination, especially, the social/communication and personal competencies are developed; (2) students are capable of dealing with a complex and ambiguous problem, if properly guided. Four conditions were identified; (3) most students are not conscious of their learning, but are able to reflect if properly encouraged; and (4) improving engineering education should be considered as an organisational learning process.
Full Text Available incineration units. The trials showed that all of the units could be used to render medical waste non-infectious, and to destroy syringes or render needles unsuitable for reuse. Emission loads from the incinerators are higher than large-scale commercial...
Turner, Katrina M; Percival, John; Kessler, David; Donovan, Jenny
The way in which pragmatic trials are designed suggests that there are differences between the experiences of participants randomised to usual care and intervention arms. These potential differences relate not only to which treatment participants receive but also how they access and engage with their allocated treatment. Such differences could affect trial results. The aim of this study was to assess whether such differences exist and, if they do, to consider their implications for the design of future trials. Interview transcripts were sampled from data sets gathered during three qualitative studies, all of which had been nested within large, primary care depression trials. Each study had explored trial participants' views and experiences of treatments received following randomisation. Transcripts from 37 participants were purposefully sampled, 20 of which were from interviews held with individuals allocated to receive usual GP care. Data were analysed thematically. There was evidence of differences between trial arms across all three data sets. Intervention participants were willing and able to engage with the treatment to which they had been allocated. Randomisation had led to them embarking upon a clear treatment pathway and receiving care in a context where they felt comfortable discussing their mental health and had sufficient time to do so. Intervention participants also had continuity with and confidence in the practitioners they saw. A few usual-care participants talked about having continuity with and confidence in their GPs. However, most of the usual-care participants reported a reluctance to consult GPs about mental health, difficulties in securing treatment appointments, and little or no changes in care following randomisation. Additionally, most reported a lack of continuity of care and a lack confidence in the treatment available to them. There are important differences between usual-care and intervention arms that go beyond treatment received, and
Elias, Merrill F; Torres, Rachael V; Davey, Adam
Randomized controlled trials of blood pressure (BP) lowering and antihypertensive medication use on cognitive outcomes have often been disappointing, reporting mixed findings and small effect sizes. We evaluate the extent to which cognitive assessment protocols used in these trials approach state-of-the-art. Overall, we find that a primary focus on cognition and the systematic selection of cognitive outcomes across trials take a backseat to other trial goals. Twelve trials investigating change in cognitive functioning were examined and none met criteria for state-of-the-art assessment, including use of at least 4 tests indexing 2 cognitive domains. Four trials investigating incident dementia were also examined. Each trial used state-of-the-art diagnostic criteria to assess dementia, although follow-up periods were relatively short, with only 2 trials lasting for at least 3 years. Weaknesses in each trial may act to obscure or weaken the positive effects of BP lowering on cognitive functioning. Improving trial designs in terms of cognitive outcomes selected and length of follow-up periods employed could lead to more promising findings. We offer logical steps to achieve state-of-the-art assessment protocols, with examples, in hopes of improving future trials.
Burridge, Jane H; Haugland, Morten; Pickering, Ruth M
OBJECTIVE: To evaluate a selective implantable drop foot stimulator (ActiGait) in terms of effect on walking and safety. DESIGN: A phase II trial in which a consecutive sample of participants acted as their own controls. SUBJECTS: People who had suffered a stroke at least 6 months prior to recrui......OBJECTIVE: To evaluate a selective implantable drop foot stimulator (ActiGait) in terms of effect on walking and safety. DESIGN: A phase II trial in which a consecutive sample of participants acted as their own controls. SUBJECTS: People who had suffered a stroke at least 6 months prior...... to recruitment and had a drop-foot that affected walking were recruited from 3 rehabilitation centres in Denmark. METHODS: Stimulators were implanted into all participants. Outcome measures were range of ankle dorsiflexion with stimulation and maximum walking speed and distance walked in 4 minutes. Measurements...
Fixsen, D L; Phillips, E L; Wolf, M M
One of the goals of many treatment programs for pre-delinquent youths is the development of the skills involved in the democratic decision-making process. At Achievement Place, one aspect of the treatment program is a semi-self-government system whereby the seven pre-delinquent youths can democratically establish many of their own rules of behavior, monitor their peers' behavior to detect violations of their rules, and conduct a "trial" to determine a rule violator's guilt or innocence, and to determine the consequences for a youth who violates a rule. Two experiments were carried out to determine the role of some of the procedures in the boys' participation in the self-government system. Experiment I showed that more boys participated in the discussion of consequences for a rule violation when they had complete responsibility for setting the consequence during the trials than when the teaching-parents set the consequence for each rule violation before the trial. An analysis of the rule violations in this experiment indicated that the boys in Achievement Place reported more of the rule violations that resulted in trials than reported by the teaching-parents or school personnel. The boys reported rule violations that occurred in the community and school as well as at Achievement Place, including most of the serious rule violations that came to the attention of the teaching-parents. In Experiment II, the results indicated that more trials were called when the teaching-parents were responsible for calling trials on rule violations reported by the peers than when the boys were responsible for calling trials. When the youths earned points for calling trials the average number of trials per day increased, but more trivial rule violations were reported. These results suggest that aspects of the democratic decision-making process in a small group of pre-delinquents can be studied and variables that affect participation can be identified and evaluated.
Hung, H M James; Wang, Sue-Jane; Yang, Peiling; Jin, Kun; Lawrence, John; Kordzakhia, George; Massie, Tristan
There are several challenging statistical problems identified in the regulatory review of large cardiovascular (CV) clinical outcome trials and central nervous system (CNS) trials. The problems can be common or distinct due to disease characteristics and the differences in trial design elements such as endpoints, trial duration, and trial size. In schizophrenia trials, heavy missing data is a big problem. In Alzheimer trials, the endpoints for assessing symptoms and the endpoints for assessing disease progression are essentially the same; it is difficult to construct a good trial design to evaluate a test drug for its ability to slow the disease progression. In CV trials, reliance on a composite endpoint with low event rate makes the trial size so large that it is infeasible to study multiple doses necessary to find the right dose for study patients. These are just a few typical problems. In the past decade, adaptive designs were increasingly used in these disease areas and some challenges occur with respect to that use. Based on our review experiences, group sequential designs (GSDs) have borne many successful stories in CV trials and are also increasingly used for developing treatments targeting CNS diseases. There is also a growing trend of using more advanced unblinded adaptive designs for producing efficacy evidence. Many statistical challenges with these kinds of adaptive designs have been identified through our experiences with the review of regulatory applications and are shared in this article.
Nelson, P. Jr.
It is argued that variational synthesis with discontinuous trial functions requires variational principles applicable to equations involving operators acting between distinct Hilbert spaces. A description is given of a Roussopoulos-type variational principle generalized to cover this situation. This principle is suggested as the basis for a unified approach to the derivation of variational functionals. In addition to esthetics, this approach has the advantage that the mathematical details increase the understanding of the derived functional, particularly the sense in which a synthesized solution should be regarded as an approximation to the true solution. By way of illustration, the generalized Roussopoulos principle is applied to derive a class of first-order diffusion functionals which admit trial functions containing approximations at an interface. These ''asymptotic'' interface quantities are independent of the limiting approximations from either side and permit use of different trial spectra at and on either side of an interface. The class of functionals derived contains as special cases both the Lagrange multiplier method of Buslik and two functionals of Lambropoulos and Luco. Some numerical results for a simple two-group model confirm that the ''multipliers'' can closely approximate the appropriate quantity in the region near an interface. (U.S.)
Smed, Marie; Schultz, Carsten; Getz, Kenneth A.
The collaboration with medical professionals in pharmaceutical clinical trials facilitates opportunities to gain valuable market information concerning product functionality issues, as well as issues related to market implementation and adoption. However, previous research on trial management lacks......’ information transfer ability, their methods of communicating, are included. The model is studied on a unique dataset of 395 medical site representatives by applying Rasch scale modeling to differentiate the stickiness of the heterogenic information issues. The results reveal that economic measures...... a differentiated perspective on the potential for information transfer from site to producer. An exploration of the variation in stickiness of information, and therefore the complexity of information transfer in clinical trials, is the main aim of this study. To further enrich the model of the dispersed sites...
Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy
The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.
K-M. Beeh (Kai-Michael); B. Hederer (Bettina); T. Glaab (Thomas); A. Müller (Achim); M.P.M.H. Rutten-van Mölken (Maureen); S. Kesten (Steven); C. Vogelmeier (Claus)
textabstractAbstract Currently available long-acting inhaled bronchodilators (tiotropium, salmeterol, formoterol) have demonstrated beneficial effects on exacerbations in placebo-controlled trials. However, there have been no direct comparisons of these drugs with exacerbations as the primary
Parkinson, Jim; Garfinkel, Sarah; Critchley, Hugo; Dienes, Zoltan; Seth, Anil K
Volitional action and self-control-feelings of acting according to one's own intentions and in being control of one's own actions-are fundamental aspects of human conscious experience. However, it is unknown whether high-level cognitive control mechanisms are affected by socially salient but nonconscious emotional cues. In this study, we manipulated free choice decisions to act or withhold an action by subliminally presenting emotional faces: In a novel version of the Go/NoGo paradigm, participants made speeded button-press responses to Go targets, withheld responses to NoGo targets, and made spontaneous, free choices to execute or withhold the response for Choice targets. Before each target, we presented emotional faces, backwards masked to render them nonconscious. In Intentional trials, subliminal angry faces made participants more likely to voluntarily withhold the action, whereas fearful and happy faces had no effects. In a second experiment, the faces were made supraliminal, which eliminated the effects of angry faces on volitional choices. A third experiment measured neural correlates of the effects of subliminal angry faces on intentional choice using EEG. After replicating the behavioural results found in Experiment 1, we identified a frontal-midline theta component-associated with cognitive control processes-which is present for volitional decisions, and is modulated by subliminal angry faces. This suggests a mechanism whereby subliminally presented "threat" stimuli affect conscious control processes. In summary, nonconscious perception of angry faces increases choices to inhibit, and subliminal influences on volitional action are deep seated and ecologically embedded.
Vandergraaf, T.T.; Drew, D.J.; Ticknor, K.V.; Hamon, C.J.
were detected in water collected from this block over the duration of the experiment. This observation is consistent with the observations for the smaller block. Results obtained from the post-migration analysis of the flow field in the 1-m 3 block were similar to those obtained in the trial block, although some anomalous behavior of the injected 237 Np was observed - this radionuclide was found to concentrate at a depth of about 30 cm. The location where the 237 Np was concentrated coincides with that of a mineralogically different layer. The migration experiment under saturated conditions was performed with a flow rate of 10 mL/hr for a duration of 600 days. The redox conditions in the block, as measured in the outflow from the block, became chemically reducing. Microbial activity has been identified as a possible cause of these chemically reducing conditions. As a consequence, strong, time-dependent attenuation of the injected 95m Tc was observed. This transport behavior was in strong contrast to that observed under unsaturated conditions. If it can be shown that chemically reducing conditions exist in the saturated zone, then a considerable amount of credit can be assigned to the saturated zone to act as a geochemical barrier to the transport of multivalent radionuclides from the repository. (author)
In the paper by the chairwoman of the Czech nuclear regulatory authority, the history of Czech nuclear legislation is outlined, the reasons for the amendment of the Atomic Act (Act No. 18/1997) are explained, and the amendments themselves are highlighted. The Act No. 13/2002 of 18 December 2001 is reproduced from the official Collection of Acts of the Czech Republic in the facsimile form. The following acts were thereby amended: Atomic Act No. 18/1997, Metrology Act No. 505/1990, Public Health Protection Act No. 258/2000, and Act No. 2/1969 on the Establishment of Ministries and Other Governmental Agencies of the Czech Republic. (P.A.)
... FEDERAL RESERVE SYSTEM 12 CFR Part 261a [Docket No. R-1313] Privacy Act of 1974; Privacy Act... implementing the Privacy Act of 1974 (Privacy Act). The primary changes concern the waiver of copying fees... records under the Privacy Act; the amendment of special procedures for the release of medical records to...
Learn about the Privacy Act of 1974, the Electronic Government Act of 2002, the Federal Information Security Management Act, and other information about the Environmental Protection Agency maintains its records.
Lawton, Julia; Snowdon, Claire; Morrow, Susan; Norman, Jane E; Denison, Fiona C; Hallowell, Nina
Recruiting and consenting women to peripartum trials can be challenging as the women concerned may be anxious, in pain, and exhausted; there may also be limited time for discussion and decision-making to occur. To address these potential difficulties, we undertook a qualitative evaluation of the internal pilot of a trial (Got-it) involving women who had a retained placenta (RP). We explored the experiences and views of women and staff about the information and consent pathway used within the pilot, in order to provide recommendations for use in future peripartum trials involving recruitment in emergency situations. In-depth interviews were undertaken with staff (n = 27) and participating women (n = 22). Interviews were analysed thematically. The accounts of women and staff were compared to identify differences and similarities in their views about recruitment and consent procedures. Women and staff regarded recruitment as having been straightforward and facilitated by the use of simplified (verbal and written) summaries of trial information. Both parties, however, conveyed discordant views about whether fully informed consent had been obtained. These differences in perspectives appeared to arise from the different factors and considerations impinging on women and staff at the time of recruitment. While staff placed emphasis on promoting understanding in the emergency situation of RP by imparting information in clear and succinct ways, women highlighted the experiential realities of their pre- and post-birthing situations, and how these had led to quick decisions being made without full engagement with the potential risks of trial participation. To facilitate informed consent, women suggested that trial information should be given during the antenatal period, and, in doing so, articulated a rights-based discourse. Staff, however, voiced opposition to this approach by emphasising a duty of care to all pregnant women, and raising concerns about causing undue
Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua
BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir, are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may...... eradicate hepatitis C virus (HCV) from the blood (sustained virological response). Sustained virological response (SVR) is used by investigators and regulatory agencies as a surrogate outcome for morbidity and mortality, based solely on observational evidence. However, there have been no randomised trials...... hepatitis C-related morbidity, serious adverse events, and health-related quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and SVR. We...
Co-curator of ACTS 2014 together with Rasmus Holmboe, Judith Schwarzbart and Sanne Kofoed. ACTS is the Museum of Contemporary Art’s international bi-annual festival. ACTS was established in 2011 and, while the primary focus is on sound and performance art, it also looks toward socially oriented art....... For the 2014 festival, the museum has entered into a collaboration with the Department for Performance Design at Roskilde University – with continued focus on sound and performance art, and social art in public spaces. With ACTS, art moves out of its usual exhibition space and instead utilizes the city, its...... various possibilities and public spaces as a stage. ACTS takes place in and around the museum and diverse locations in Roskilde city. ACTS is partly curated by the museum staff and partly by guest curators. ACTS 2014 is supported by Nordea-fonden and is a part of the project The Museum goes downtown....
Zimmermann, C; Baldo, C; Molino, A
To examine the effects of framing of outcome and probabilities of cancer occurrence on the treatment preference which breast cancer patients indicate for hypothetical patient scenarios. A modified version of the Decision Board Instrument (Levine et al. 1992) was administered to 35 breast cancer patients with past ACT experience. Patients expressed their choice regarding ACT for six scenarios which were characterized by either negative or positive framing of outcome and by one of the three levels of probability of recurrence (high, medium, low). The framing had no influence on ACT choices over all three probability levels. The majority chose ACT for high and medium risk and one third switched from ACT to No ACT in the low-risk condition. This switch was statistically significant. Hypothetical treatment decisions against ACT occur only when the probability of recurrence is low and the benefit of ACT is small. This finding for patients with past experience of ACT is similar to those reported for other oncological patient groups still in treatment.
Adam, Laura M; Manca, Donna P
Background Recruitment is often a difficult and costly part of any human research study. Social media and other emerging means of mass communication hold promise as means to complement traditional strategies used for recruiting participants because they can reach a large number of people in a short amount of time. With the ability to target a specified audience, paid Facebook advertisements have potential to reach future research participants of a specific demographic. This paper describes the experiences of a randomized controlled trial in Edmonton, Alberta, attempting to recruit healthy pregnant women between 8 and 20 weeks’ gestation for participation in a prenatal study. Various traditional recruitment approaches, in addition to paid Facebook advertisements were trialed. Objective To evaluate the effectiveness of paid advertisements on Facebook as a platform for recruiting pregnant women to a randomized controlled trial in comparison with traditional recruitment approaches. Methods Recruitment using traditional approaches occurred for 7 months, whereas Facebook advertisements ran for a total of 26 days. Interested women were prompted to contact the study staff for a screening call to determine study eligibility. Costs associated with each recruitment approach were recorded and used to calculate the cost to recruit eligible participants. Performance of Facebook advertisements was monitored using Facebook Ads Manager. Results Of the 115 women included, 39.1% (n=45) of the women who contacted study staff heard about the study through Facebook, whereas 60.9% (n=70) of them heard about it through traditional recruitment approaches. During the 215 days (~7 months) that the traditional approaches were used, the average rate of interest was 0.3 (0.2) women/day, whereas the 26 days of Facebook advertisements resulted in an average rate of interest of 2.8 (1.7) women/day. Facebook advertisements cost Can $506.91 with a cost per eligible participant of Cad $20.28. In
Ahmed, Asma; Felmlee, Daniel J
There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.
Crampton, Suzanne M.; Hodge, John W.; Mishra, Jitendra M.
Analysis by decade of the effects of the Equal Pay Act of 1963 shows that women's earnings relative to men's increased by 10 cents from 1960-1990. Black and Hispanic women's earnings lagged further behind. More education and experience did not help women narrow the gap. (SK)
COPD-SEAT will be one of the first trials aimed at reducing sedentary behaviour at home in patients hospitalised for an acute exacerbation of COPD. This trial will provide valuable insight into the feasibility of implementing an at-home technology-based feedback intervention for reducing sedentary behaviour into patients existing care. Findings will inform a future large-scale trial acting as an adjuvant to pulmonary rehabilitation.
Full Text Available Abstract Background Recruitment to randomized controlled trials is known to be challenging. It is important to understand and identify predictors of good or poor accrual to a clinical trial so that appropriate strategies can be put in place to overcome these problems and facilitate successful trial completion. We have developed a survey tool to establish the recruitment experience of clinical teams regarding facilitators and barriers to recruitment in a clinical trial and describe herein the method of developing the questionnaire. Methods A literature search was conducted to identify studies that have explored facilitators and barriers to recruitment, and a list of potential factors affecting recruitment to a clinical trial was generated. These factors were categorized in terms relating to the (i trial, (ii site, (iii patient, (iv clinical team, (v information and consent and (vi study team. A list was provided for responders to grade these factors as weak, intermediate or strong facilitators or barriers to recruitment. Results A web-based survey questionnaire was developed. This survey was designed to establish the recruitment experience of clinical teams with regard to the perceived facilitators and barriers to recruitment, to identify strategies applied to overcome these problems, and to obtain suggestions for change in the organization of future trials. The survey tool can be used to assess the recruitment experience of clinical teams in a single/multicenter trial in any clinical setting or speciality involving adults or children either in an ongoing trial or at trial completion. The questionnaire is short, easy to administer and to complete, with an estimated completion time of 11 minutes. Conclusions We have presented a robust methodology for developing this survey tool that provides an evidence-based list of potential factors that can affect recruitment to a clinical trial. We recommend that all clinical trialists should consider using
An Act to establish a Nuclear Regulatory Authority in Ghana. This Act provides for the regulation and management of activities and practices for the peaceful use of nuclear material or energy, and to provide for the protection of persons and the environment against the harmful effects of radiation; and to ensure the effective implementation of the country’s international obligations and for related matters. This Act replaced the Radiation Protection Instrument, of 1993 (LI 1559).
(g) a collective agreement in terms of Section 213 of the Labour Relations Act. 59 ..... "Direct marketing" means to approach a person, either in person or by ..... literacy skills and minimal experience as a consumer, to understand the contents.
Anguzu, Ronald; Akun, Pamela R; Ogwang, Rodney; Shour, Abdul Rahman; Sekibira, Rogers; Ningwa, Albert; Nakamya, Phellister; Abbo, Catherine; Mwaka, Amos D; Opar, Bernard; Idro, Richard
A large amount of preparation goes into setting up trials. Different challenges and lessons are experienced. Our trial, testing a treatment for nodding syndrome, an acquired neurological disorder of unknown cause affecting thousands of children in Eastern Africa, provides a unique case study. As part of a study to determine the aetiology, understand pathogenesis and develop specific treatment, we set up a clinical trial in a remote district hospital in Uganda. This paper describes our experiences and documents supportive structures (enablers), challenges faced and lessons learned during set-up of the trial. Protocol development started in September 2015 with phased recruitment of a critical study team. The team spent 12 months preparing trial documents, procurement and training on procedures. Potential recruitment sites were pre-visited, and district and local leaders met as key stakeholders. Key enablers were supportive local leadership and investment by the district and Ministry of Health. The main challenges were community fears about nodding syndrome, adverse experiences of the community during previous research and political involvement. Other challenges included the number and delays in protocol approvals and lengthy procurement processes. This hard-to-reach area has frequent power and Internet fluctuations, which may affect cold chains for study samples, communication and data management. These concerns decreased with a pilot community engagement programme. Experiences and lessons learnt can reduce the duration of processes involved in trial-site set-up. A programme of community engagement and local leader involvement may be key to the success of a trial and in reducing community opposition towards participation in research.
Gold, Paul B; Meisler, Neil; Santos, Alberto B; Carnemolla, Mark A; Williams, Olivia H; Keleher, Jennie
Urban-based randomized clinical trials of integrated supported employment (SE) and mental health services in the United States on average have doubled the employment rates of adults with severe mental illness (SMI) compared to traditional vocational rehabilitation. However, studies have not yet explored if the service integrative functions of SE will be effective in coordinating rural-based services that are limited, loosely linked, and geographically dispersed. In addition, SE's ability to replicate the work outcomes of urban programs in rural economies with scarce and less diverse job opportunities remains unknown. In a rural South Carolina county, we designed and implemented a program blending Assertive Community Treatment (ACT) with an SE model, Individual Placement and Support (IPS). The ACT-IPS program operated with ACT and IPS subteams that tightly integrated vocational with mental health services within each self-contained team. In a 24-month randomized clinical trial, we compared ACT-IPS to a traditional program providing parallel vocational and mental health services on competitive work outcomes for adults with SMI (N = 143; 69% schizophrenia, 77% African American). More ACT-IPS participants held competitive jobs (64 versus 26%; p < .001, effect size [ES] = 0.38) and earned more income (median [Mdn] = $549, interquartile range [IQR] = $0–$5,145, versus Mdn = $0, IQR = $0–$40; p < .001, ES = 0.70) than comparison participants. The competitive work outcomes of this rural ACT-IPS program closely resemble those of urban SE programs. However, achieving economic self-sufficiently and developing careers probably require increasing access to higher education and jobs imparting marketable technical skills. PMID:16177278
Kemal Sinan Özmen
Full Text Available This study follows three pre-service teachers during three academic semesters in which they took an acting course for teachers and participated in practicum with a special focus on rehearsing and developing their teacher identities. In order to create the necessary context for them, an acting course for pre-service teacher education was designed in parallel with a model which is based on an influential acting theory. This model, namely the BEING (Believe, Experiment, Invent, Navigate, Generate, was also designed by the researcher. The incentive behind designing a model grounded on acting literature was that the relevant literature does not provide trainers with a universal model which can be referred as a manual for running and monitoring acting courses for teachers. In this case study, this model was also tested in terms of its applicability and functionality in practice. Based on analyses of audio taped interviews, session journals and reflections, the five stages of the BEING Model was found to be highly applicable and functional in terms of reflecting the natural development process of teacher identity development. Pre-service teachers displayed a significant development in communication skills and professional identities. Therefore, the BEING model provides a perspective and a philosophy of benefiting from acting literature for teacher educators with little or no knowledge on acting and theatre
Kemal Sinan Özmen
Full Text Available This study follows three pre-service teachers during three academic semesters in which they took an acting course for teachers and participated in practicum with a special focus on rehearsing and developing their teacher identities. In order to create the necessary context for them, an acting course for pre-service teacher education was designed in parallel with a model which is based on an influential acting theory. This model, namely the BEING (Believe, Experiment, Invent, Navigate, Generate, was also designed by the researcher. The incentive behind designing a model grounded on acting literature was that the relevant literature does not provide trainers with a universal model which can be referred as a manual for running and monitoring acting courses for teachers. In this case study, this model was also tested in terms of its applicability and functionality in practice. Based on analyses of audio taped interviews, session journals and reflections, the five stages of the BEING Model was found to be highly applicable and functional in terms of reflecting the natural development process of teacher identity development. Pre-service teachers displayed a significant development in communication skills and professional identities. Therefore, the BEING model provides a perspective and a philosophy of benefiting from acting literature for teacher educators with little or no knowledge on acting and theatre.
Vera Lucia da Silva
Full Text Available This article introduces the Animal Act provisions about animal testing. At first, it was proposed a bioethical and biolaw theoretical approach. Following, it was mentioned the Arouca Law, current norm that rules the Article 225 on the Federal Constitution, and authorizes experiments on animals. Then was introduced some elements of the Bills in proceeding at the Senate aimed at changing the Arouca Law. The point is to present an interpretation that focus on a wider view of the Animal Act protective aspect, especially concerning animal testing.
Paige, H.W.; Owens, J.E.
This paper is based on a report prepared by International Energy Associates Limited (IEAL) under contract to the Department of Energy. The report, whose title is the same as that of this paper, was submitted to DOE a little over one year ago. In that report, the relevant provisions of the Nuclear Waste Policy Act of 1982 setting forth the procedures for obtaining the local acceptance of sites for nuclear waste facilities were compared with the corresponding procedures of fifteen foreign countries also trying to locate sites for nuclear waste facilities. In this paper, the major points on which the Nuclear Waste Policy Act is or is not in keeping with lessons learned in other countries are discussed as well as some general and specific observations related to siting acceptance problems and how the Act addresses them
Full Text Available Abstract Background Polycystic liver disease (PLD is defined as having more than 20 liver cysts and can present as a severe and disabling condition. Most symptoms are caused by the mass effect of the liver size and include abdominal pain and distension. The somatostatin analogues octreotide and lanreotide have proven to reduce polycystic liver volume. mTOR inhibitors such as everolimus inhibit cell proliferation and might thereby reduce growth of liver cysts. This trial aims to assess the benefit of combination therapy of everolimus and octreotide compared to octreotide monotherapy. In this study we present the structure of the trial and the characteristics of the included patients. Methods/design This is a randomized open-label clinical trial comparing the effect of 12 months of everolimus and octreotide to octreotide monotherapy in PLD patients. Primary outcome is change in liver volume determined by CT-volumetry. Secondary outcomes are changes in abdominal symptoms and quality of life. Moreover, safety and tolerability of the drugs will be assessed. Discussion This trial will compare the relative efficacy of combination therapy with octreotide and everolimus to octreotide monotherapy. Since they apply to different pathways of cystogenesis we expect that combining octreotide and everolimus will result in a cumulative reduction of polycystic liver volume. Trial registration number ClinicalTrials.gov: NCT01157858
Oberdieck, Fernando G.
In the autoshaping preparation subjects are exposed to magazine training (US-only trials) prior to the conditioning phase in which a stimulus (conditioned stimulus, CS) predicts the delivery of a response independent reinforcer (unconditioned stimulus, US). Two experiments examined the hypothesis that irrespective of the number of US-only trials administered the magazine training and autoshaping contexts interact to determine conditioning, as measured by contact responses to the CS. The conte...
Davidson, K M; Tyrer, P; Tata, P; Cooke, D; Gumley, A; Ford, I; Walker, A; Bezlyak, V; Seivewright, H; Robertson, H; Crawford, M J
Little information exists on treatment effectiveness in antisocial personality disorder (ASPD). We investigated the feasibility and effectiveness of carrying out a randomized controlled trial of cognitive behaviour therapy (CBT) in men with ASPD who were aggressive. This was an exploratory two-centre, randomized controlled trial in a community setting. Fifty-two adult men with a diagnosis of ASPD, with acts of aggression in the 6 months prior to the study, were randomized to either treatment as usual (TAU) plus CBT, or usual treatment alone. Change over 12 months of follow-up was assessed in the occurrence of any act of aggression and also in terms of alcohol misuse, mental state, beliefs and social functioning. The follow-up rate was 79%. At 12 months, both groups reported a decrease in the occurrence of any acts of verbal or physical aggression. Trends in the data, in favour of CBT, were noted for problematic drinking, social functioning and beliefs about others. CBT did not improve outcomes more than usual treatment for men with ASPD who are aggressive and living in the community in this exploratory study. However, the data suggest that a larger study is required to fully assess the effectiveness of CBT in reducing aggression, alcohol misuse and improving social functioning and view of others. It is feasible to carry out a rigorous randomized controlled trial in this group.
Charoen, Saovapong; Eemsiri, Jaruratana; Sajjabut, Surasak
Full text: The objectives of the experiment were to disseminate irradiated retail foods to the domestic publics and to test consumer acceptance on irradiated ground chilli and ground pepper. Market trials of irradiated ground chilli and ground pepper were carried out at 2 local markets and 4 in Bangkok and Nontaburi in 2005-2007. Before the start of the experiment, processing room, gamma irradiation room and labels of the products were approved by Food and Drug Administration, Thailand. 50 grams of irradiated products were packaged in plastic bags for the market trials. 688 and 738 bags of ground chilli and ground pepper were sold, respectively. Questionnaires distributed with the products were commented by 59 consumers and statistically analyzed by experimental data pass program. 88.1 and 91.4 percents of the consumers were satisfied with the quality and the price, respectively. 79.7% of the consumers chose to buy irradiated ground chilli and ground pepper because they believed that the quality of irradiated products were better than that of non-irradiated ones. 91.5% of the consumers would certainly buy irradiated chilli and pepper again. Through these market trials, it was found that all of the products were sold out and the majority of the consumers who returned the questionnaires was satisfied with the irradiated ground chilli and ground pepper and also had good attitude toward irradiated foods
Yadavaia, James E; Hayes, Steven C; Vilardaga, Roger
Self-compassion has been shown to be related to several types of psychopathology, including traumatic stress, and has been shown to improve in response to various kinds of interventions. Current conceptualizations of self-compassion fit well with the psychological flexibility model, which underlies acceptance and commitment therapy (ACT). However, there has been no research on ACT interventions specifically aimed at self-compassion. This randomized trial therefore compared a 6-hour ACT-based workshop targeting self-compassion to a wait-list control. From pretreatment to 2-month follow-up, ACT was significantly superior to the control condition in self-compassion, general psychological distress, and anxiety. Process analyses revealed psychological flexibility to be a significant mediator of changes in self-compassion, general psychological distress, depression, anxiety, and stress. Exploratory moderation analyses revealed the intervention to be of more benefit in terms of depression, anxiety, and stress to those with greater trauma history.
Doby, Brianna L; Tobian, Aaron A R; Segev, Dorry L; Durand, Christine M
The HIV Organ Policy Equity (HOPE) Act, signed in 2013, reversed the federal ban on HIV-to-HIV transplantation. In this review, we examine the progress in HOPE implementation, the current status of HIV-to-HIV transplantation, and remaining challenges. Pursuant to the HOPE Act, the Department of Health and Human Services revised federal regulations to allow HIV-to-HIV transplants under research protocols adherent to criteria published by the National Institutes of Health. The first HIV-to-HIV kidney and liver transplants were performed at Johns Hopkins in March of 2016. Legal and practical challenges remain. Further efforts are needed to educate potential HIV+ donors and to support Organ Procurement Organizations. As of November 2017, there are 22 transplant centers approved to perform HIV-to-HIV transplants in 10 United Network for Organ Sharing regions. To date, 16 Organ Procurement Organizations in 22 states have evaluated HIV+ donors. The National Institutes of Health-funded HOPE in Action: A Multicenter Clinical Trial of HIV-to-HIV Deceased Donor (HIVDD) Kidney Transplantation Kidney Trial will launch at 19 transplant centers in December of 2017. A HOPE in Action Multicenter HIVDD Liver Trial is in development. Significant progress toward full HOPE implementation has been made though barriers remain. Some challenges are unique to HIV-HIV transplantation, whereas others are amplifications of issues across the current transplant system. In addition to a public health benefit for all transplant candidates in the United States, partnership on the HOPE Act has the potential to address systemic challenges to national donation and transplantation.
Aventin, Áine; Lohan, Maria; Maguire, Lisa; Clarke, Mike
The move toward evidence-based education has led to increasing numbers of randomised trials in schools. However, the literature on recruitment to non-clinical trials is relatively underdeveloped, when compared to that of clinical trials. Recruitment to school-based randomised trials is, however, challenging, even more so when the focus of the study is a sensitive issue such as sexual health. This article reflects on the challenges of recruiting post-primary schools, adolescent pupils and parents to a cluster randomised feasibility trial of a sexual-health intervention, and the strategies employed to address them. The Jack Trial was funded by the UK National Institute for Health Research. It comprised a feasibility study of an interactive film-based sexual-health intervention entitled If I Were Jack, recruiting over 800 adolescents from eight socio-demographically diverse post-primary schools in Northern Ireland. It aimed to determine the facilitators and barriers to recruitment and retention to a school-based sexual-health trial and identify optimal multi-level strategies for an effectiveness study. As part of an embedded process evaluation, we conducted semi-structured interviews and focus groups with principals, vice-principals, teachers, pupils and parents recruited to the study as well as classroom observations and a parents' survey. With reference to social learning theory, we identified a number of individual-, behavioural- and environmental-level factors that influenced recruitment. Commonly identified facilitators included perceptions of the relevance and potential benefit of the intervention to adolescents, the credibility of the organisation and individuals running the study, support offered by trial staff, and financial incentives. Key barriers were prior commitment to other research, lack of time and resources, and perceptions that the intervention was incompatible with pupil or parent needs or the school ethos. Reflecting on the methodological
Hubbard, Gill; Campbell, Anna; Davies, Zoe; Munro, Julie; Ireland, Aileen V; Leslie, Stephen; Watson, Angus Jm; Treweek, Shaun
Recruitment to randomised controlled trials (RCTs) is a perennial problem. Calls have been made for trialists to make recruitment performance publicly available. This article presents our experience of recruiting to a pilot RCT of cardiac rehabilitation for patients with bowel cancer with an embedded process evaluation. Recruitment took place at three UK hospitals. Recruitment figures were based on the following: i) estimated number of patient admissions, ii) number of patients likely to meet inclusion criteria from clinician input and iii) recruitment rates in previous studies. The following recruitment procedure was used:Nurse assessed patients for eligibility.Patients signed a screening form indicating interest in and agreement to be approached by a researcher about the study.An appointment was made at which the patient signed a consent form and was randomised to the intervention or control group. Information about all patients considered for the study and subsequently included or excluded at each stage of the recruitment process and reasons given were recorded. There were variations in the time taken to award Research Management approval to run the study at the three sites (45-359 days). Sixty-two percent of the original recruitment estimate was reached. The main reason for under-recruitment was due to over-estimation of the number of patient admissions; other reasons were i) not assessing all patients for eligibility, ii) not completing a screening form for eligible patients and iii) patients who signed a screening form being lost to the study before consenting and randomisation. Pilot trials should not simply aim to improve recruitment estimates but should also identify factors likely to influence recruitment performance in a future trial and inform the development of that trial's recruitment strategies. Pilot trials are a crucial part of RCT design. Nevertheless, pilot trials are likely to be small scale, involving only a small number of sites, and
Healy, Patricia; Galvin, Sandra; Williamson, Paula R; Treweek, Shaun; Whiting, Caroline; Maeso, Beccy; Bray, Christopher; Brocklehurst, Peter; Moloney, Mary Clarke; Douiri, Abdel; Gamble, Carrol; Gardner, Heidi R; Mitchell, Derick; Stewart, Derek; Jordan, Joan; O'Donnell, Martin; Clarke, Mike; Pavitt, Sue H; Guegan, Eleanor Woodford; Blatch-Jones, Amanda; Smith, Valerie; Reay, Hannah; Devane, Declan
Despite the problem of inadequate recruitment to randomised trials, there is little evidence to guide researchers on decisions about how people are effectively recruited to take part in trials. The PRioRiTy study aimed to identify and prioritise important unanswered trial recruitment questions for research. The PRioRiTy study - Priority Setting Partnership (PSP) included members of the public approached to take part in a randomised trial or who have represented participants on randomised trial steering committees, health professionals and research staff with experience of recruiting to randomised trials, people who have designed, conducted, analysed or reported on randomised trials and people with experience of randomised trials methodology. This partnership was aided by the James Lind Alliance and involved eight stages: (i) identifying a unique, relevant prioritisation area within trial methodology; (ii) establishing a steering group (iii) identifying and engaging with partners and stakeholders; (iv) formulating an initial list of uncertainties; (v) collating the uncertainties into research questions; (vi) confirming that the questions for research are a current recruitment challenge; (vii) shortlisting questions and (viii) final prioritisation through a face-to-face workshop. A total of 790 survey respondents yielded 1693 open-text answers to 6 questions, from which 1880 potential questions for research were identified. After merging duplicates, the number of questions was reduced to 496. Questions were combined further, and those that were submitted by fewer than 15 people and/or fewer than 6 of the 7 stakeholder groups were excluded from the next round of prioritisation resulting in 31 unique questions for research. All 31 questions were confirmed as being unanswered after checking relevant, up-to-date research evidence. The 10 highest priority questions were ranked at a face-to-face workshop. The number 1 ranked question was "How can randomised trials become
Crichton Georgina E
Full Text Available Abstract Background There are many challenges involved in running randomised controlled dietary intervention trials that investigate health outcomes. The aim of this paper was to evaluate the recruitment process, retention of participants and challenges faced in our dairy intervention trial, and to provide strategies to combat the difficulties of running long-term dietary intervention trials. Methods A 12-month, randomised, two-way crossover study was conducted in overweight adults with habitually low dairy food consumption to assess the effects of a high dairy intake (4 servings of reduced-fat dairy per day compared with a low dairy intake (1 serving of reduced-fat dairy per day on measures of cardiometabolic and cognitive health. On completion of the high dairy intake phase, each participant was interviewed about their experience in the trial and responses were used to evaluate the key issues for study participants. Results Although the recruitment target was achieved, high rates of attrition (49.3% and difficulties maintaining participant compliance (reported by 37.8% of participants were major threats to the viability of the study. Factors that contributed to the high attrition included inability to comply with the dietary requirements of the study protocol (27.0%, health problems or medication changes (24.3% and time commitment (10.8%. Conclusion Attrition and adherence to study requirements present challenges to trials requiring longer-term dietary change. Including a run-in period to further assess the motivation, commitment and availability of participants, maintaining regular contact with participants during control phases, minimising time commitment, providing flexibility with dietary requirements, facilitating positive experiences, and stringent monitoring of diet are some key recommendations for future dietary intervention trials. Trial registration Australia and New Zealand Clinical Trials Registry (ACTRN 12608000538347
Paganoni, Sabrina; Nicholson, Katharine; Chan, James; Shui, Amy; Schoenfeld, David; Sherman, Alexander; Berry, James; Cudkowicz, Merit; Atassi, Nazem
Urate has been identified as a predictor of amyotrophic lateral sclerosis (ALS) survival in some but not all studies. Here we leverage the recent expansion of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to study the association between urate levels and ALS survival. Pooled data of 1,736 ALS participants from the PRO-ACT database were analyzed. Cox proportional hazards regression models were used to evaluate associations between urate levels at trial entry and survival. After adjustment for potential confounders (i.e., creatinine and body mass index), there was an 11% reduction in risk of reaching a survival endpoint during the study with each 1-mg/dL increase in uric acid levels (adjusted hazard ratio 0.89, 95% confidence interval 0.82-0.97, P ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. Muscle Nerve 57: 430-434, 2018. © 2017 Wiley Periodicals, Inc.
Moreno, Lucas; Vaidya, Sucheta J; Pinkerton, C Ross; Lewis, Ian J; Imeson, John; Machin, David; Pearson, Andrew D J
Therapy for high-risk neuroblastoma is intensive and multimodal, and significant long-term adverse effects have been described. The aim of this study was to identify the nature and severity of late complications of metastatic neuroblastoma survivors included in the ENSG5 clinical trial. The trial protocol included induction chemotherapy (randomized "Standard" OPEC/OJEC vs. "Rapid" COJEC), surgery of primary tumor and high-dose melphalan with stem cell rescue. Two hundred and sixty-two children were randomized, 69 survived >5 years, and 57 were analyzed. Data were obtained from the ENSG5 trial database and verified with questionnaires sent to participating centers. Median follow-up was 12.9 (6.9-16.5) years. No differences were found in late toxicities between treatment arms. Twenty-eight children (49.1%) developed hearing loss. Nine patients (15.8%) developed glomerular filtration rate <80 ml/min/1.73 m(2), but no cases of chronic renal failure were documented. Endocrine complications (28.1% of children) included mainly hypogonadism and delayed growth. Four children developed second malignancies, three of them 5 years after diagnosis: one osteosarcoma, one carcinoma of the parotid gland and one ependymoma. There were no hematological malignancies or deaths in remission. This study analyzed a wide cohort of high-risk neuroblastoma survivors from a multi-institutional randomized trial and established the profile of long-term toxicity within the setting of an international clinical trial. Copyright © 2012 Wiley Periodicals, Inc.
Rayi, Appaji; Thompson, Stephanie; Gloss, David; Malhotra, Konark
To explore the evidence of reporting bias among completed epilepsy intervention trials (EITs) and compliance of applicable EITs to Food and Drug Administration Amendments Act (FDAAA). We included consecutive EITs registered as completed on ClinicalTrials.gov from 2008 to 2015. Descriptive data was collected including study type, study phase, funding source, primary completion date, and result reporting date. Time to result reporting was analyzed using Kaplan-Meier estimates for two time periods (2008-2011 and 2012-2015). PubMed, Web of Science, and Google scholar databases were manually searched for publication details. Overall, 95/126 EITs (75%) reported, while remaining 31/126 (25%) did not report their results. Time to reporting was significantly lower for trials completed during 2012-2015 (16.5 months; 95% CI: 13.60-19.40; p = .002; Cohen's d = 0.68) as compared to the trials completed during 2008-2011 (25.9 months; 95% CI: 21.56-30.22). 72/126 trials were conducted in at least one U.S. center. 56/72 (78%) of the trials met the FDAAA criteria, while only 19/56 (34%) reported within the mandated one-year time frame. The lack of reporting of nearly one-quarter of completed epilepsy intervention trials suggests existence of reporting bias. As such, it should be considered an important criterion for determining risk of bias in epilepsy systematic reviews. Copyright © 2018 Elsevier B.V. All rights reserved.
Crittenden, Marka; Kohrt, Holbrook; Levy, Ronald; Jones, Jennifer; Camphausen, Kevin; Dicker, Adam; Demaria, Sandra; Formenti, Silvia
Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an abscopal effect. Granulocyte-macrophage colony-stimulating factor was administered during radiotherapy to a metastatic site in patients with metastatic solid tumors to translate evidence obtained in a murine model of syngeneic mammary carcinoma treated with cytokine FLT-3L and radiation. Subsequent clinical availability of vaccines and immune checkpoint inhibitors has triggered a wave of enthusiasm for testing them in combination with radiotherapy. Examples of ongoing clinical trials are described in this report. Importantly, most of these trials include careful immune monitoring of the patients enrolled and will generate important data about the proimmunogenic effects of radiation in combination with a variety of immune modulators, in different disease settings. Results of these studies are building a platform of evidence for radiotherapy as an adjuvant to immunotherapy and encourage the growth of this novel field of radiation oncology. Copyright © 2015 Elsevier Inc. All rights reserved.
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false 1940 Act and 1980 Act Companies. 107.115 Section 107.115 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS... Companies. A 1940 Act or 1980 Act Company is eligible to apply for an SBIC license, and an existing Licensee...
Guillemin, Marilys; Barnard, Emma; Walker, Hannah; Bennell, Kim; Hinman, Rana; Gillam, Lynn
This study explored participants' experiences of randomized controlled trial (RCT) participation to examine their understanding of the trial design and whether their consent was indeed informed. A nested qualitative interview study was conducted with 38 participants from a sample of 282 who participated in a complex RCT evaluating the effectiveness of laser compared with needle acupuncture for chronic knee pain. Overall participants had a good understanding of the RCT, and concepts such as randomization and placebo. Their experiences of being in the trial were largely positive, even if they did not experience any knee pain improvement. Their responses to unblinding at the end of the study were accepting. Participants had a good functional understanding of the RCT, sufficient for valid informed consent. © The Author(s) 2015.
Cafferty, F H; Coyle, C; Rowley, S; Berkman, L; MacKensie, M; Langley, R E
Opportunities to enter patients into more than one clinical trial are not routinely considered in cancer research and experiences with co-enrolment are rarely reported. Potential benefits of allowing appropriate co-enrolment have been identified in other settings but there is a lack of evidence base or guidance to inform these decisions in oncology. Here, we discuss the benefits and challenges associated with co-enrolment based on experiences in the Add-Aspirin trial - a large, multicentre trial recruiting across a number of tumour types, where opportunities to co-enrol patients have been proactively explored and managed. The potential benefits of co-enrolment include: improving recruitment feasibility; increased opportunities for patients to participate in trials; and collection of robust data on combinations of interventions, which will ensure the ongoing relevance of individual trials and provide more cohesive evidence to guide the management of future patients. There are a number of perceived barriers to co-enrolment in terms of scientific, safety and ethical issues, which warrant consideration on a trial-by-trial basis. In many cases, any potential effect on the results of the trials will be negligible - limited by a number of factors, including the overlap in trial cohorts. Participant representatives stress the importance of autonomy to decide about trial enrolment, providing a compelling argument for offering co-enrolment where there are multiple trials that are relevant to a patient and no concerns regarding safety or the integrity of the trials. A number of measures are proposed for managing and monitoring co-enrolment. Ensuring acceptability to (potential) participants is paramount. Opportunities to enter patients into more than one cancer trial should be considered more routinely. Where planned and managed appropriately, co-enrolment can offer a number of benefits in terms of both scientific value and efficiency of study conduct, and will increase the
Kwarteng, E. Fredua
This paper discusses the implementation of Nunavut compulsory school attendance policy as part of the Nunavut Education Act (2002). Using a bottom-up approach to policy implementation in the literature and the author's six years teaching experience in Nunavut, the paper argues that the compulsory school attendance policy may not achieve its…
Staunæs, Dorthe; Nissen, Morten
Using motivation as thinking experiment, this presentation reconstructs critical post/psychologies in the light of the futures they envision. “Post” or “critical” does not imply not being concerned with psychology (the science of experience, thinking, acting, and feeling). Rather it is an alterna......Using motivation as thinking experiment, this presentation reconstructs critical post/psychologies in the light of the futures they envision. “Post” or “critical” does not imply not being concerned with psychology (the science of experience, thinking, acting, and feeling). Rather...... it, but we do it anyway” and in four versions 1) the modern project of a unified teleology, 2) intellectual nihilism, 3) confirmation of prevailing liberal pragmatics; 4) return to premodern ethics. Not appealing. Is there a fifth way? We are not sure, but we have embarked on a search guided...
McDougall, Sanders A; Pothier, Alexandria G; Der-Ghazarian, Taleen; Herbert, Matthew S; Kozanian, Olga O; Castellanos, Kevin A; Flores, Ana T
During adulthood, associative learning is necessary for the expression of one-trial behavioral sensitization; however, it is uncertain whether the same associative processes are operative during the preweanling period. Two strategies were used to assess the importance of associative learning for one-trial behavioral sensitization of preweanling rats. In the initial experiments, we varied both the sequence and time interval between presentation of the conditioned stimulus (CS, novel environment) and unconditioned stimulus (US, cocaine). In the final experiment, we determined whether electroconvulsive shock-induced retrograde amnesia would disrupt one-trial behavioral sensitization. Results showed that robust-sensitized responding was apparent regardless of the sequence in which cocaine and the novel environment (the presumptive CS) were presented. Varying the time between CS and US presentation (0, 3, or 6 h) was also without effect. Results from experiment 3 showed that single or multiple electroconvulsive shock treatments did not alter the expression of the sensitized response. Therefore, these data indicated that one-trial behavioral sensitization of preweanling rats was exclusively mediated by nonassociative mechanisms and that associative processes did not modulate sensitized responding. These findings are in contrast to what is observed during adulthood, as adult rats exhibit one-trial behavioral sensitization only when associative processes are operative.
Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida
The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763
Rahbar, Mohammad H; Dickerson, Aisha S; Cai, Chunyan; Pedroza, Claudia; Hessabi, Manouchehr; Shen, Loren; Pandurengan, Renganayaki; Jacobs, Amber Nicole M; Indupuru, Hari; Sline, Melvin R; Delgado, Rigoberto I; Macdonald, Claire; Ford, Gary A; Grotta, James C; Barreto, Andrew D
We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of Argatroban in Combination with Recombinant Tissue Plasminogen Activator for Acute Stroke (ARTSS-2). ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of Argatroban injection (low, high) in combination with recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as hemorrhage after thrombolysis (HAT) score and presence of distal internal carotid artery occlusion (DICAO). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 patients enrolled in ARTSS-2, we evaluated performance of our randomization program using chi-square tests of homogeneity or extended Fisher's exact test. We also designed a four-step partly Bayesian safety stopping rule for low and high dose Argatroban arms. Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), HAT score (0-2 vs. 3-5, P=1.0), and DICAO (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose Argatroban were not crossed. Despite challenges, data quality was assured. We recommend adaptive designs for randomization and Bayesian safety stopping rules for multisite Phase I/II RCTs for maintaining additional flexibility. Efficient data coordination could lead to improved data quality. Copyright © 2015. Published by Elsevier Inc.
Rey-Mermet, Alodie; Meier, Beat
The purpose of the present study was to determine how long-lasting the post-conflict slowing following incongruent stimuli is. In previous research, incongruent stimuli have been used to induce a conflict because they have relevant features for two different response alternatives. So far, the post-conflict slowing following incongruent stimuli has mainly been assessed up to one trial. In the first two experiments, we assessed the persistence of the post-conflict slowing across several trials. To this end, we presented a few incongruent stimuli among non-conflict stimuli. The results showed a consistent slowing for the first few trials immediately following the incongruent trials. In addition, a sporadic slowing was still found on later trials. In two subsequent experiments, we investigated to what extent the infrequency of incongruent trials - rather than their conflict - induced this slowing. To determine this, we used the same design as in the first two experiments, but we presented non-conflict stimuli as infrequent stimuli. The results showed a slowing on one subsequent trial, ruling out the possibility that the post-conflict slowing following incongruent trials was only caused by infrequency. Together, the findings of the present study indicate that the conflict induced by incongruent trials can have a longer lasting impact on subsequent trials than previously thought.
Stefaniak Victoria J
Full Text Available Abstract Background An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI. During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI. Methods Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors. Results Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients. Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness. However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified. Conclusions Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post
Oza Amit M
Full Text Available Abstract Background There is a paucity of literature on the referral outcome of patients seen in phase I trial clinics in academic oncology centres. This study aims to provide information on the accrual rate and to identify obstacles in the recruitment process. Methods A retrospective chart review was performed for all new patients referred and seen in the phase I clinic at the Princess Margaret Hospital between January 2000 and June 2005. Data on their demographics, medical history, and details of trial participation or non-entry were recorded. Results A total of 667 new phase I referrals were seen during the stated period. Of these patients, 197 (29.5% patients were enrolled into a phase I trial, and 64.5% of them started trial within 1 month of the initial visit. About a quarter (165 of 667 of the patients referred were deemed ineligible at their first visit, with the most frequent reasons for ineligibility being poor performance status, unacceptable bloodwork, too many prior treatments and rapid disease progression. The remaining 305 patients (45.7% were potentially eligible at their initial visit, but never entered a phase I trial. The main reasons for their non-entry were patient refusal, other treatment recommended first, and lack of available trials or trial spots. Conclusion This study provides information on the clinical realities underlying a referral to a phase I clinic and eventual trial enrollment. Better selection of patients, appropriate education of referring physicians, and opening phase I trials with fewer restrictions on some criteria such as prior therapy may enhance their recruitment rates.
Lu Wei; Li Yanhao; Dusan Pavcnik
Objective: To evaluate the efficiency of percutaneously placed bioprosthetic bicuspid venous valve (BVV) in the treatment of deep vein insufficiency in animal experiments and clinical trials. Methods: BVV was made of two pieces of lyophilized porcine small intestinal submucosa(SIS) which were attached to a stent frame. Three kinds of BVVs (BVV1, BVV2, BVV3) was developed using different kinds of stent frames and different methods of attachment. BVV1, BVV2 and BVV3 were percutaneously placed into ovine's jugular veins acrossed the nature valves. Ascending and descending angiography were performed before and after' BVVs placement. The patency of veins and the function of valves was evaluated during 5 weeks to 6 months follow-up. In clinical trial, BVV1 and BVV3 were percutaneously placed into 3 and 15 patients with chronic venous insufficiency (CVI) respectively. The patency of veins and the function of valves was also evaluated during 1 to 3 years' follow-up. Results: In animal experiment, BVV1, BVV2, and BVV3 were placed to 24, 26 and 12 ovine's jugular veins respectively. During 5 weeks to 6 months follow- up period, 22 (88.0%), 24(92.3%) and 12 of the BVVs exhibited good function. Endothelium of both surfaces of SIS leaflets was complete in approximately 3 months. SIS was gradually reabsorbed and replaced by the host's own cells. Three BVV1 were placed into 3 patients with CVI. At the third years follow-up, symptoms relieved in 2 cases and no change of clinical symptoms was found in 1 patient. BVV3 were percutaneously placed into 15 patients with advanced symptomatic CVI. At one month and 3 months' follow- up after BVV3 placement, all BVV3 functioned well. However, BVV3 were flexible and functioned well in only 4 cases at 1 year' s follow-up. Intravascular ultrasound revealed thickened rigid cusps with valve leakage of different levels and no symptom resolved in 11 cases. Conclusions: Percutaneous implantation of bioprosthetic BVV is a promising method in the
Kenyon, Sara; Taylor, David J
To estimate the short term effect of the publication of a major clinical trial on clinical practise. Questionnaire survey of clinical practise. UK. All maternity units in the UK. A self-administered questionnaire completed by lead consultants on delivery suite of maternity units. Changes in antibiotic prescription. Within six months of publication, approximately 50% of maternity units had changed their guidelines for the care of women with preterm prelabour rupture of the fetal membranes. Publication of a major clinical trial does impact on clinical practise but the impact is heterogeneous in terms of time and consistency.
A summary on the trial run a 1,300 MW PWR and the following nuclear tests is given. Further a series of experiments to approve the specified performance and the fitness of safety devices are described. (orig.) [de
Rodrigues, H. C. M. L.; Deprest, J.; v. d. Berg, P. P.
Objective In this article, we reflect on whether randomized controlled trials (RCTs) are adequate for the clinical evaluation of maternal-fetal surgery for congenital diaphragmatic hernia (CDH), focusing on the role of patients' preferences in the setting up of research protocols, on the requirement
Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho; Kim, Tae Won
Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and
This paper explores how performance culture could affect students' learning about, and disposition towards, acting as organisational change agents in schools. This is based on findings from an initiative aimed to enable students to experience acting as change agents on an aspect of the school's culture that concerned them. The initiative was…
Smed, Marie; Getz, Kenneth A.
in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract...... Research Organization) and thereby adding another link in the relationships between site and sponsor. These changes are intended to optimize the time-consuming and costly trial phases; however, there is a need to study whether valuable knowledge and experience is compromised in the process. Limited......' knowledge gained in clinical trials is utilized by the industry. Responses from 451 global investigative site representatives are included in the study. The analysis of the extensive dataset reveals that the current processes of collaboration between sites and the industry restrict the leverage of valuable...
GaL, P.; Adamica, T.; Marosik, V.; Rehak, A.
In this paper authors describe the experience gained during commissioning and trial operation of Mochovce NPP (EMO). The first year of EMO operation from the point of view of safety and reliability was successful. Evidently we were challenged with certain problems characteristic to this stage of operation which resulted in automatic reactor shutdown. There were 11 automatic shutdowns in 1998 by action of the quick emergency protection AO-1 and two manual shutdowns by the AO-1 key. In 1999, there were 6 automatic shutdowns by action of the quick emergency protection AO-1. Three of them was connected to the falsely activated binary signal of MCP switch of, in two cases the reason came out from the turbo-generator (TG) cooling water system. Very positive trend in the operation of both units shows the fact that during all commissioning period of the second unit there were only three automatic reactor shutdowns by the signal AO-1. All these actions were done in frame of commissioning tests. All causes which activated the automatic unit shutdowns were found out and rectified, the overall tuning of the cooling water system is on the process now. The solution of this problem is possible only power commissioning, and in the stage of the trial operation had no direct impacts on the nuclear, radiation, or technical safety respectively. In 1998 two events according to the INES scale after second unit commissioning because of two unit links of the cooling water system. The operational events during the commissioning tests, start-up tests, physical commissioning, were ranked the category 1 ('Action of SIS U040 p po <8,34 MPa at the system 2 and 3' and 'Breaching the L and C'). In 1999 only events occurred that were ranked in the category safety insignificant events and lower (category 0, or off the scale respectively). In the frame of the safety culture principles adopted, such as critical attitude, exact and careful approach, and communication, these problems were given the
... Freedom of Information Act and Privacy Act Procedures AGENCY: Special Inspector General for Afghanistan... Freedom of Information Act (FOIA) and the Privacy Act of 1974. These procedures will facilitate public..., Freedom of information, Privacy. Authority and Issuance For the reasons set forth above, SIGAR establishes...
Smith, Orla M; McDonald, Ellen; Zytaruk, Nicole; Foster, Denise; Matte, Andrea; Clarke, France; Meade, Laurie; O'Callaghan, Nicole; Vallance, Shirley; Galt, Pauline; Rajbhandari, Dorrilyn; Rocha, Marcelo; Mehta, Sangeeta; Ferguson, Niall D; Hall, Richard; Fowler, Robert; Burns, Karen; Qushmaq, Ismael; Ostermann, Marlies; Heels-Ansdell, Diane; Cook, Deborah
Successful completion of randomized trials depends upon efficiently and ethically screening patients and obtaining informed consent. Awareness of modifiable barriers to obtaining consent may inform ongoing and future trials. The objective of this study is to describe and examine determinants of consent rates in an international heparin thromboprophylaxis trial (Prophylaxis for ThromboEmbolism in Critical Care Trial, clinicaltrials.gov NCT00182143). Throughout the 4-year trial, research personnel approached eligible critically ill patients or their substitute decision makers for informed consent. Whether consent was obtained or declined was documented daily. The trial was conducted in 67 centers in 6 countries. A total of 3764 patients were randomized. The overall consent rate was 82.2% (range, 50%-100%) across participating centers. Consent was obtained from substitute decision makers and patients in 90.1% and 9.9% of cases, respectively. Five factors were independently associated with consent rates. Research coordinators with more experience achieved higher consent rates (odds ratio [OR], 3.43; 95% confidence interval, 2.42-4.86; P 10 years of experience). Consent rates were higher in smaller intensive care units with less than 15 beds compared with intensive care units with 15 to 20 beds, 21 to 25 beds, and greater than 25 beds (all ORs, <0.5; P < .001) and were higher in centers with more than 1 full-time research staff (OR, 1.95; 95% confidence interval, 1.28-2.99; P < .001). Consent rates were lower in centers affiliated with the Canadian Critical Care Trials Group or the Australian and New Zealand Intensive Care Society Clinical Trials Group compared with other centers (OR, 0.57; 95% confidence interval, 0.42-0.77; P < .001). Finally, consent rates were highest during the pilot trial, lowest during the initiation of the full trial, and increased over years of recruitment (P < .001). Characteristics of study centers, research infrastructure, and experience
Srivastav, Aditi; Fairbrother, Gerry; Simpson, Lisa A
Adverse childhood experiences (ACEs) occur when children are exposed to trauma and/or toxic stress and may have a lifelong effect. Studies have shown that ACEs are linked with poor adult health outcomes and could eventually raise already high health care costs. National policy interest in ACEs has recently increased, as many key players are engaged in community-, state-, and hospital-based efforts to reduce factors that contribute to childhood trauma and/or toxic stress in children. The Affordable Care Act (ACA) has provided a promising foundation for advancing the prevention, diagnosis, and management of ACEs and their consequences. Although the ACA's future is unclear and it does not adequately address the needs of the pediatric population, many of the changes it spurred will continue regardless of legislative action (or inaction), and it therefore remains an important component of our health care system and national strategy to reduce ACEs. We review ways in which some of the current health care policy initiatives launched as part of the implementation of the ACA could accelerate progress in addressing ACEs by fully engaging and aligning various health care stakeholders while recognizing limitations in the law that may cause challenges in our attempts to improve child health and well-being. Specifically, we discuss coverage expansion, investments in the health workforce, a family-centered care approach, increased access to care, emphasis on preventive services, new population models, and improved provider payment models. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.
Ljungberg, Amanda; Denhov, Anne; Topor, Alain
Although being personal in relationships with service users is commonly described as an important aspect of the way that professionals help people with severe mental problems, this has also been described to bring with it a need to keep a distance and set boundaries. This study aims to explore how professionals working in psychiatric care view being personal in their relationships with users. Qualitative interviews with 21 professionals working in three outpatient psychiatric units, analyzed through thematic analysis. Being personal in their relationships with users was described as something that participants regarded to be helpful, but that also entails risks. Participants described how they balanced being personal by keeping a distance and maintaining boundaries in their relationships based on their "experience-based knowledge" to counter these risks. While these boundaries seemed to play an important part in the way that they act and behave, they were not seen as fixed, but rather as flexible and dynamic. Boundaries could sometimes be transgressed to the benefit of users. Being personal was viewed as something that may be helpful to users, but that also entails risks. Although boundaries may be a useful concept for use in balancing these risks, they should be understood as something complex and flexible.
Full Text Available Martha Sajatovic,1,2 Ruth Ross,3 Susan N Legacy,4 Matthew Byerly,5 John M Kane,6,7 Faith DiBiasi,8 Heather Fitzgerald,9 Christoph U Correll6,7 1Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 2Departments of Psychiatry and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Ross Editorial, Port Townsend, WA, USA; 4US Medical Affairs Neuroscience, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 5Cell Biology and Neuroscience, Center for Mental Health Research and Recovery, Montana State University, Bozeman, MT, USA; 6Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY, USA; 7Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Glen Oaks, NY, USA; 8Scientific Communications, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA; 9Medical Affairs, Lundbeck LLC, Deerfield, IL, USA Objective: The aim of this study was to provide recommendations on initiating and maintaining long-acting injectable antipsychotics (LAIs in individuals with schizophrenia/schizoaffective or bipolar disorder. Methods: A 50-question survey comprising 916 response options was completed by 34 expert researchers and high prescribers with extensive LAI experience, rating relative appropriateness/importance on a 9-point scale. Consensus was determined using chi-square test of score distributions. Results of 21 questions comprising 339 response options regarding LAI initiation, maintenance treatment, adequate trial definition, identifying treatment nonresponse, and switching are reported. Results: Experts agreed that the most important LAI selection factor was patient response/tolerability to previous antipsychotics. An adequate therapeutic LAI trial was defined as the time to steady state ± 1–2 injection cycles. Experts suggested that oral efficacy and tolerability should be established before switching to an
Williamson, Rebecca A.; Meltzoff, Andrew N.
Young children learn from others’ examples, and they do so selectively. We examine whether the efficacy of prior experiences influences children’s imitation. Thirty-six-month-olds had initial experience on a causal learning task either by performing the task themselves or by watching an adult perform it. The nature of the experience was manipulated such that the actor had either an easy or a difficult experience completing the task. Next, a second adult demonstrated an innovative technique fo...
Carlezon, William A; Krystal, Andrew D
Kappa-opioid receptor (KOR) antagonists are currently being considered for the treatment of a variety of neuropsychiatric conditions, including depressive, anxiety, and substance abuse disorders. A general ability to mitigate the effects of stress, which can trigger or exacerbate these conditions, may explain their putative efficacy across such a broad array of conditions. The discovery of their potentially therapeutic effects evolved from preclinical research designed to characterize the molecular mechanisms by which experience causes neuroadaptations in the nucleus accumbens (NAc), a key element of brain reward circuitry. This research established that exposure to drugs of abuse or stress increases the activity of the transcription factor CREB (cAMP response element binding protein) in the NAc, which leads to elevated expression of the opioid peptide dynorphin that in turn causes core signs of depressive- and anxiety-related disorders. Disruption of KORs-the endogenous receptors for dynorphin-produces antidepressant- and anxiolytic-like actions in screening procedures that identify standard drugs of these classes, and reduces stress effects in tests used to study addiction and stress-related disorders. Although interest in this target is high, prototypical KOR antagonists have extraordinarily persistent pharmacodynamic effects that complicate clinical trials. The development of shorter acting KOR antagonists together with more rapid designs for clinical trials may soon provide insight on whether these drugs are efficacious as would be predicted by preclinical work. If successful, KOR antagonists would represent a unique example in psychiatry where the therapeutic mechanism of a drug class is understood before it is shown to be efficacious in humans. © 2016 Wiley Periodicals, Inc.
Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.
...; (5) Responsibility for testing, test equipment and normal operation and maintenance during the trial... Telephone Systems of RUS Borrowers,” RUS Bulletin 344-2. When new items of materials or equipment are... modifications that its suitability cannot be determined based on laboratory data and/or field experience, a...
... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (11-092)] Privacy Act of 1974; Privacy Act... retirement of one Privacy Act system of records notice. SUMMARY: In accordance with the Privacy Act of 1974, NASA is giving notice that it proposes to cancel the following Privacy Act system of records notice...
Knorr, Ulla; Vinberg, Maj; Hansen, Allan
Introduction The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether long-ter...
Levin, Michael E.; Potts, Sarah; Haeger, Jack; Lillis, Jason
Weight self-stigma is a promising target for innovative interventions seeking to improve outcomes among overweight/obese individuals. Preliminary research suggests acceptance and commitment therapy (ACT) may be an effective approach for reducing weight self-stigma, but a guided self-help version of this intervention may improve broad dissemination. This pilot open trial sought to evaluate the potential acceptability and efficacy of a guided self-help ACT intervention, included coaching and a ...
Schroll, Jeppe Bennekou; Penninga, Elisabeth I; Gøtzsche, Peter C
BACKGROUND: Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe......Med and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about...
Preventing recurrence of endometriosis by means of long-acting progestogen therapy (PRE-EMPT): report of an internal pilot, multi-arm, randomised controlled trial incorporating flexible entry design and adaption of design based on feasibility of recruitment.
Middleton, Lee J; Daniels, Jane P; Weckesser, Annalise; Bhattacharya, Siladitya
Endometriosis is associated with the growth of endometrium in ectopic sites mainly within the pelvis. This results in inflammation and scarring, causing pain and impaired quality of life. Endometriotic lesions can be excised or ablated surgically, but the risk of recurrence is high. A Heath Technology Assessment commissioning call in 2011 sought applications for trials aimed at evaluating long-term effectiveness of postoperative, long-acting, reversible contraceptives (LARCs) in preventing recurrence of endometriosis. A survey of gynaecologists indicated that there was no consensus about which LARC (Levonorgestrel Intrauterine System (LNG-IUS) or depot medroxyprogesterone acetate injection (DMPA)) or comparator (combined oral contraceptive pill (COCP) or no treatment) should be evaluated. Hence, we designed a 'flexible-entry' internal pilot to assess whether a four-arm trial was feasible including a possible design adaption based on pilot findings. In this pilot, women could be randomised to two, three or four treatment options provided that one was a LARC and one was a non-LARC. An assessment of feasibility based on recruitment to these options and a revised substantive trial design was considered by an independent oversight committee. The study ran for 1 year from April 2014 and 77 women were randomised. Only 5 (6%) women accepted randomisation to all groups, with 63 (82%) having a LARC preference and 55 (71%) a non-LARC preference. Four-way and three-way designs were ruled out with a two-way LARC versus COCP design, stratified by prerandomisation choice of LARC and optional subrandomisation to LNG-IUS versus DMPA considered a feasible substantive study. Multi-arm studies are potentially efficient as they can answer multiple questions simultaneously but are difficult to recruit to if there are strong patient or clinician preferences. A flexible approach to randomisation in a pilot phase can be used to assess feasibility of such studies and modify a trial design
Knorr, Ulla Benedichte Søsted; Vinberg, Maj; Hansen, Allan
Abstract Introduction: The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether...
Cognitive architectures have often been applied to data from individual experiments. In this paper, I develop an ACT-R reader that can model a much larger set of data, eye-tracking corpus data. It is shown that the resulting model has a good fit to the data for the considered low-level processes. Unlike previous related works (most prominently, Engelmann, Vasishth, Engbert & Kliegl, ), the model achieves the fit by estimating free parameters of ACT-R using Bayesian estimation and Markov-Chain Monte Carlo (MCMC) techniques, rather than by relying on the mix of manual selection + default values. The method used in the paper is generalizable beyond this particular model and data set and could be used on other ACT-R models. Copyright © 2017 Cognitive Science Society, Inc.
Full Text Available Abstract Background Qualitative methods are increasingly used to study the process of clinical trials and patients understanding of the rationale for trials, randomisation and reasons for taking part or refusing. Patients' understandings are inevitably influenced by the recruiting clinician's understanding of the trial, yet relatively little qualitative work has explored clinicians' perceptions and understandings of trials. This study interviewed surgeons shortly after the multi-centre, pragmatic RCT in which they had participated had been completed. Methods We used in-depth interviews with surgeons who participated in the Spine Stabilisation Trial (a pragmatic RCT to explore their understanding of the trial purpose and how this understanding had influenced their recruitment procedures and interpretation of the results. A purposive sample of eleven participating surgeons was chosen from 8 of the 15 UK trial centres. Results Although the surgeons thought that the trial was addressing an important question there was little agreement about what this question was: although it was a trial of 'equivalent' treatments, some thought that it was a trial of surgery, others a trial of rehabilitation and others that it was exploring what to do with patients in whom all other treatment options had been unsuccessful. The surgeons we interviewed were not aware of the rationale for the pragmatic inclusion criteria and nearly all were completely baffled about the meaning of 'equipoise'. Misunderstandings about the entry criteria were an important source of confusion about the results and led to reluctance to apply the results to their own practice. Conclusion The study suggests several lessons for the conduct of future multi-centre trials. Recruiting surgeons (and other clinicians may not be familiar with the rationale for pragmatic designs and may need to be regularly reminded about the purpose during the study. Reassurance may be necessary that a pragmatic
Hamlet draws us into its rendered world, enabling us to experience it with depth, awareness, and resonance, in a mode we recognize as aesthetic. By way of Shakespeare's play--primarily the first act--and a detailed case study, aesthetic and psychoanalytic experience are compared, to suggest that, for our own analytic discourse, we revalue Freud's unease that his case studies read like short stories.
Ghaffari, Farzaneh; Naseri, Mohsen; Jafari Hajati, Razieh; Zargaran, Arman
Medical history explains that Persian physicians used scientific methods based on clinical experiences and observations for treatment from pre-Islamic time (before 637 AD) and centuries later (in the Islamic era). Rhazes was one of the Persian physicians acknowledged as a pharmacist, chemist and prominent scientific writer on various subjects of medicine and philosophy. In this study, we aimed to investigate clinical experiences, as well as the ethical and critical views of Rhazes in medical practice. Rhazes promoted ethics in the medical profession. He expressed critical key points about ancient written texts. He broke ancient physicians' taboos in medical theories and evaluated them based on his own experiences. He designed animal and preclinical evaluations for his theories and also performed the first clinical trials with control groups in the history. His critical views about medical sciences as well as his beliefs in experiments resulted in many medical, chemical and pharmaceutical findings. Therefore, in history, he can be considered as the pioneer in using trials and experiments for approving medical methods.
Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer.
Clark, C H; Miles, E A; Urbano, M T Guerrero; Bhide, S A; Bidmead, A M; Harrington, K J; Nutting, C M
The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.
A. E. Karateev
Full Text Available The widespread use of parenteral chondroprotectors is a feature of Russian medical practice. There are many drugs of this series in a Russian physician's arsenal, including chondroitin sulfate (CS, glucosamine sulfate (GS, glycosaminoglycan-peptide complex, and bioactive concentrate from small sea fish for intramuscular injections. The paper analyzes Russian trials of the efficacy and safety of two injectable formulations of CS and GS (ICS and IGS. ICS was tested in 17 articles containing a total of 1639 patients with osteoarthritis (OA, non-specific back pain (NBP, or shoulder fractures and pain after stroke. Standard therapy (NSAIDs + physiotherapy served as a control in the majority of the paper. In these trials, the reductions in visual analog scale (VAS and WOMAC pain in OA treated with ICS averaged 58.2±22.3% and those were 26.1±14.7% in the control groups; the reductions in VAS NBP reached an average of 87.1±16.8 and 62.2±21.7%, respectively. ICS also showed a good effect in shoulder fractures and pain after a stroke. The number of local adverse reactions after injections was insignificant (4.4%; they did not threaten the health of patients and they caused ICS to be discontinued only in 3 cases. IGS was investigated in two trials (n=154, which confirmed its efficacy (total pain relief >50% and relative safety. Thus, the data of Russian trials suggest that ICS and IGS have good therapeutic potential and favorable tolerance.
Langston, Anne L; McCallum, Marilyn; Campbell, Marion K; Robertson, Clare; Ralston, Stuart H
Although, consumer involvement in individual studies is often limited, their involvement in guiding health research is generally considered to be beneficial. This paper outlines our experiences of an integrated relationship between the organisers of a clinical trial and a consumer organisation. The PRISM trial is a UK multicentre, randomized controlled trial comparing treatment strategies for Paget's disease of the bone. The National Association for the Relief of Paget's Disease (NARPD) is the only UK support group for sufferers of Paget's disease and has worked closely with the PRISM team from the outset. NARPD involvement is integral to the conduct of the trial and specific roles have included: peer-review; trial steering committee membership; provision of advice to participants, and promotion of the trial amongst Paget's disease patients. The integrated relationship has yielded benefits to both the trial and the consumer organisation. The benefits for the trial have included: recruitment of participants via NARPD contacts; well-informed participants; unsolicited patient advocacy of the trial; and interested and pro-active collaborators. For the NARPD and Paget's disease sufferers, benefits have included: increased awareness of Paget's disease; increased access to relevant health research; increased awareness of the NARPD services; and wider transfer of diagnosis and management knowledge to/from health care professionals. Our experience has shown that an integrated approach between a trial team and a consumer organisation is worthwhile. Adoption of such an approach in other trials may yield significant improvements in recruitment and quality of participant information flow. There are, however, resource implications for both parties.
Braun, Daniel A.; Aertsen, Ad; Paz, Rony; Vaadia, Eilon; Rotter, Stefan; Mehring, Carsten
When faced with unpredictable environments, the human motor system has been shown to develop optimized adaptation strategies that allow for online adaptation during the control process. Such online adaptation is to be contrasted to slower over-trial learning that corresponds to a trial-by-trial update of the movement plan. Here we investigate the interplay of both processes, i.e., online adaptation and over-trial learning, in a visuomotor experiment performed by macaques. We show that simple non-adaptive control schemes fail to perform in this task, but that a previously suggested adaptive optimal feedback control model can explain the observed behavior. We also show that over-trial learning as seen in learning and aftereffect curves can be explained by learning in a radial basis function network. Our results suggest that both the process of over-trial learning and the process of online adaptation are crucial to understand visuomotor learning. PMID:21720526
Marquardsen, Mikkel; Ogden, Michelle; Gøtzsche, Peter C
Objective To describe the redactions in contemporary protocols for industry-sponsored randomised drug trials with patient relevant outcomes and to evaluate whether there was a legitimate rationale for the redactions. Design Cohort study. Under the Freedom of Information Act, we requested access to trial protocols approved by a research ethics committee in Denmark from October 2012 to March 2013. We received 17 consecutive protocols, which had been redacted before we got them, and nine protocols without redactions. In five additional cases, the companies refused to let the committees give us access, and in three other cases, documents were missing. Participants Not applicable. Setting Not applicable. Main outcome measure Amount and nature of redactions in 22 predefined key protocol variables. Results The redactions were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials: data analysis, handling of missing data, detection and analysis of adverse events, definition of the outcomes, interim analyses and premature termination of the study, sponsor's access to incoming data while the study is running, ownership to the data and investigators' publication rights. The parts of the text that were redacted differed widely, both between companies and within the same company. Conclusions We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.
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Full Text Available ... Trial Protocol Each clinical trial has a master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The trial ... clinical trial; and detailed information about the treatment plan. Eligibility Criteria A clinical trial's protocol describes what ...
Adam, Laura M; Manca, Donna P; Bell, Rhonda C
Recruitment is often a difficult and costly part of any human research study. Social media and other emerging means of mass communication hold promise as means to complement traditional strategies used for recruiting participants because they can reach a large number of people in a short amount of time. With the ability to target a specified audience, paid Facebook advertisements have potential to reach future research participants of a specific demographic. This paper describes the experiences of a randomized controlled trial in Edmonton, Alberta, attempting to recruit healthy pregnant women between 8 and 20 weeks' gestation for participation in a prenatal study. Various traditional recruitment approaches, in addition to paid Facebook advertisements were trialed. To evaluate the effectiveness of paid advertisements on Facebook as a platform for recruiting pregnant women to a randomized controlled trial in comparison with traditional recruitment approaches. Recruitment using traditional approaches occurred for 7 months, whereas Facebook advertisements ran for a total of 26 days. Interested women were prompted to contact the study staff for a screening call to determine study eligibility. Costs associated with each recruitment approach were recorded and used to calculate the cost to recruit eligible participants. Performance of Facebook advertisements was monitored using Facebook Ads Manager. Of the 115 women included, 39.1% (n=45) of the women who contacted study staff heard about the study through Facebook, whereas 60.9% (n=70) of them heard about it through traditional recruitment approaches. During the 215 days (~7 months) that the traditional approaches were used, the average rate of interest was 0.3 (0.2) women/day, whereas the 26 days of Facebook advertisements resulted in an average rate of interest of 2.8 (1.7) women/day. Facebook advertisements cost Can $506.91 with a cost per eligible participant of Cad $20.28. In comparison, the traditional approaches
Full Text Available The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using a blockchain to prove the existence of documents describing pre-specified endpoints in clinical trials. Here, we extend the idea by using smart contracts - code, and data, that resides at a specific address in a blockchain, and whose execution is cryptographically validated by the network - to demonstrate how trust in clinical trials can be enforced and data manipulation eliminated. We show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history.
Dombernowsky, Tilde; Haedersdal, Merete; Lassen, Ulrik; Thomsen, Simon F
Clinical trial allocation in multinational pharmaceutical companies includes country selection and site selection. With emphasis on site selection, the overall aim of this study was to examine which factors pharmaceutical companies value most when allocating clinical trials. The specific aims were (1) to identify key decision makers during country and site selection, respectively, (2) to evaluate by which parameters subsidiaries are primarily assessed by headquarters with regard to conducting clinical trials, and (3) to evaluate which site-related qualities companies value most when selecting trial sites. Eleven semistructured interviews were conducted among employees engaged in trial allocation at 11 pharmaceutical companies. The interviews were analyzed by deductive content analysis, which included coding of data to a categorization matrix containing categories of site-related qualities. The results suggest that headquarters and regional departments are key decision makers during country selection, whereas subsidiaries decide on site selection. Study participants argued that headquarters primarily value timely patient recruitment and quality of data when assessing subsidiaries. The site-related qualities most commonly emphasized during interviews were study population availability, timely patient recruitment, resources at the site, and site personnel's interest and commitment. Costs of running the trials were described as less important. Site personnel experience in conducting trials was described as valuable but not imperative. In conclusion, multinational pharmaceutical companies consider recruitment-related factors as crucial when allocating clinical trials. Quality of data and site personnel's interest and commitment are also essential, whereas costs seem less important. While valued, site personnel experience in conducting clinical trials is not imperative.
Briggs, Melissa A.; Kalolella, Admirabilis; Bruxvoort, Katia; Wiegand, Ryan; Lopez, Gerard; Festo, Charles; Lyaruu, Pierre; Kenani, Mitya; Abdulla, Salim; Goodman, Catherine; Kachur, S. Patrick
Background Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. Method and Findings A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6–18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was 5 years, experience (aOR: 2.8; 95% CI: 1.2–6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5–7.4). Conclusion Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops. PMID:24732258
Thomas eFitzGerald, MD
Full Text Available The National Cancer Institute clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence based process improvements for clinical oncology patient care. The cooperative groups are undergoing a transformation process as we further integrate molecular biology into personalized patient care and move to incorporate international partners in clinical trials. To support this vision, data acquisition and data management informatics tools must become both nimble and robust to support transformational research at an enterprise level. Information, including imaging, pathology, molecular biology, radiation oncology, surgery, systemic therapy and patient outcome data needs to be integrated into the clinical trial charter using adaptive clinical trial mechanisms for design of the trial. This information needs to be made available to investigators using digital processes for real time data analysis. Future clinical trials will need to be designed and completed in a timely manner facilitated by nimble informatics processes for data management. This paper discusses both past experience and future vision for clinical trials as we move to develop data management and quality assurance processes to meet the needs of the modern trial.
Monolithic Microwave Integrated Circuit (MMIC) arrays developed by the NASA Lewis Research Center and the Air Force Rome Laboratory were demonstrated in aeronautical terminals and in mobile or fixed Earth terminals linked with NASA's Advanced Communications Technology Satellite (ACTS). Four K/Ka-band experimental arrays were demonstrated between May 1994 and May 1995. Each array had GaAs MMIC devices at each radiating element for electronic beam steering and distributed power amplification. The 30-GHz transmit array used in uplinks to ACTS was developed by Lewis and Texas Instruments. The three 20-GHz receive arrays used in downlinks from ACTS were developed in cooperation with the Air Force Rome Laboratory, taking advantage of existing Air Force integrated-circuit, active-phased-array development contracts with the Boeing Company and Lockheed Martin Corporation. Four demonstrations, each related to an application of high interest to both commercial and Department of Defense organizations, were conducted. The location, type of link, and the data rate achieved for each of the applications is shown. In one demonstration-- an aeronautical terminal experiment called AERO-X--a duplex voice link between an aeronautical terminal on the Lewis Learjet and ACTS was achieved. Two others demonstrated duplex voice links (and in one case, interactive video links as well) between ACTS and an Army high-mobility, multipurpose wheeled vehicle (HMMWV, or "humvee"). In the fourth demonstration, the array was on a fixed mount and was electronically steered toward ACTS. Lewis served as project manager for all demonstrations and as overall system integrator. Lewis engineers developed the array system including a controller for open-loop tracking of ACTS during flight and HMMWV motion, as well as a laptop data display and recording system used in all demonstrations. The Jet Propulsion Laboratory supported the AERO-X program, providing elements of the ACTS Mobile Terminal. The successful
Tedre, Matti; Moisseinen, Nella
Experiments play a central role in science. The role of experiments in computing is, however, unclear. Questions about the relevance of experiments in computing attracted little attention until the 1980s. As the discipline then saw a push towards experimental computer science, a variety of technically, theoretically, and empirically oriented views on experiments emerged. As a consequence of those debates, today's computing fields use experiments and experiment terminology in a variety of ways. This paper analyzes experimentation debates in computing. It presents five ways in which debaters have conceptualized experiments in computing: feasibility experiment, trial experiment, field experiment, comparison experiment, and controlled experiment. This paper has three aims: to clarify experiment terminology in computing; to contribute to disciplinary self-understanding of computing; and, due to computing's centrality in other fields, to promote understanding of experiments in modern science in general.
... DEPARTMENT OF AGRICULTURE Office of the Secretary Privacy Act: Revision of Privacy Act Systems of Records AGENCY: Office of the Secretary, USDA. ACTION: Notice to Revise Privacy Act Systems of Records... two Privacy Act Systems of Records entitled ``Information on Persons Disqualified from the...
Douglas H. Marin dos Santos
Full Text Available The relationship between clinical research and the pharmaceutical industry has placed clinical trials in jeopardy. According to the medical literature, more than 70% of clinical trials are industry-funded. Many of these trials remain unpublished or have methodological flaws that distort their results. In 2007, it was signed into law the Food and Drug Administration Amendments Act (FDAAA, aiming to provide publicly access to a broad range of biomedical information to be made available on the platform ClinicalTrials (available at https://www.clinicaltrials.gov. We accessed ClinicalTrials.gov and evaluated the compliance of researchers and sponsors with the FDAAA. Our sample comprised 243 protocols of clinical trials of biological monoclonal antibodies (mAb adalimumab, bevacizumab, infliximab, rituximab, and trastuzumab. We demonstrate that the new legislation has positively affected transparency patterns in clinical research, through a significant increase in publication and online reporting rates after the enactment of the law. Poorly designed trials, however, remain a challenge to be overcome, due to a high prevalence of methodological flaws. These flaws affect the quality of clinical information available, breaching ethical duties of sponsors and researchers, as well as the human right to health.
Fiore-Gartland, Andrew; Kullman, Nicholas; deCamp, Allan C; Clenaghan, Graham; Yang, Wayne; Magaret, Craig A; Edlefsen, Paul T; Gilbert, Peter B
Analysis of HIV-1 virions from participants infected in a randomized controlled preventive HIV-1 vaccine efficacy trial can help elucidate mechanisms of partial protection. By comparing the genetic sequence of viruses from vaccine and placebo recipients to the sequence of the vaccine itself, a technique called 'sieve analysis', one can identify functional specificities of vaccine-induced immune responses. We have created an interactive web-based visualization and data access tool for exploring the results of sieve analyses performed on four major preventive HIV-1 vaccine efficacy trials: (i) the HIV Vaccine Trial Network (HVTN) 502/Step trial, (ii) the RV144/Thai trial, (iii) the HVTN 503/Phambili trial and (iv) the HVTN 505 trial. The tool acts simultaneously as a platform for rapid reinterpretation of sieve effects and as a portal for organizing and sharing the viral sequence data. Access to these valuable datasets also enables the development of novel methodology for future sieve analyses. Visualization: http://sieve.fredhutch.org/viz . Source code: https://github.com/nkullman/SIEVE . Data API: http://sieve.fredhutch.org/data . firstname.lastname@example.org. © The Author(s) 2017. Published by Oxford University Press.
Marin Dos Santos, Douglas H; Atallah, Álvaro N
The relationship between clinical research and the pharmaceutical industry has placed clinical trials in jeopardy. According to the medical literature, more than 70% of clinical trials are industry-funded. Many of these trials remain unpublished or have methodological flaws that distort their results. In 2007, it was signed into law the Food and Drug Administration Amendments Act (FDAAA), aiming to provide publicly access to a broad range of biomedical information to be made available on the platform ClinicalTrials (available at https://www.clinicaltrials.gov). We accessed ClinicalTrials.gov and evaluated the compliance of researchers and sponsors with the FDAAA. Our sample comprised 243 protocols of clinical trials of biological monoclonal antibodies (mAb) adalimumab, bevacizumab, infliximab, rituximab, and trastuzumab. We demonstrate that the new legislation has positively affected transparency patterns in clinical research, through a significant increase in publication and online reporting rates after the enactment of the law. Poorly designed trials, however, remain a challenge to be overcome, due to a high prevalence of methodological flaws. These flaws affect the quality of clinical information available, breaching ethical duties of sponsors and researchers, as well as the human right to health.
Moher, Jeff; Song, Joo-Hyun
Target selection is often biased by an observer's recent experiences. However, not much is known about whether these selection biases influence behavior across different effectors. For example, does looking at a red object make it easier to subsequently reach towards another red object? In the current study, we asked observers to find the uniquely colored target object on each trial. Randomly intermixed pre-trial cues indicated the mode of action: either an eye movement or a visually guided reach movement to the target. In Experiment 1, we found that priming of popout, reflected in faster responses following repetition of the target color on consecutive trials, occurred regardless of whether the effector was repeated from the previous trial or not. In Experiment 2, we examined whether an inhibitory selection bias away from a feature could transfer across effectors. While priming of popout reflects both enhancement of the repeated target features and suppression of the repeated distractor features, the distractor previewing effect isolates a purely inhibitory component of target selection in which a previewed color is presented in a homogenous display and subsequently inhibited. Much like priming of popout, intertrial suppression biases in the distractor previewing effect transferred across effectors. Together, these results suggest that biases for target selection driven by recent trial history transfer across effectors. This indicates that representations in memory that bias attention towards or away from specific features are largely independent from their associated actions.
Cohen, M.X.; Cavanagh, J.F.
In most cognitive neuroscience experiments there are many behavioral and experimental dynamics, and many indices of brain activity, that vary from trial to trial. For example, in studies of response conflict, conflict is usually treated as a binary variable (i.e., response conflict exists or does
Mihail, Michael D.; George, Thomas F.; Feldman, Bernard J.
This article describes an experiment that measures the forces acting on a flying bird during takeoff. The experiment uses a minimum of equipment and only an elementary knowledge of kinematics and Newton's second law. The experiment involves first digitally videotaping a bird during takeoff, analyzing the video to determine the bird's position as a…
... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 13-071] Privacy Act of 1974; Privacy Act System of Records AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Privacy Act system of records. SUMMARY: Each Federal agency is required by the Privacy Act of 1974 to publish...
Full Text Available An extensive number of pathologies are associated with mitochondrial dysfunction (MDF and oxidative stress (OS. Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN, such as α-lipoic acid (ALA, Coenzyme Q10 (CoQ10, and l-carnitine (CARN (or its derivatives have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluated for the following endpoints: (a treated diseases; (b dosages, number of enrolled patients and duration of treatment; (c trial success for each MN or MN combinations as reported by authors. The reports satisfying the above endpoints included total numbers of trials and frequencies of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with “classical” antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN, suggesting forthcoming clinical studies. The criteria in study design and monitoring MN-based clinical trials are discussed.
Pagano, Giovanni; Aiello Talamanca, Annarita; Castello, Giuseppe; Cordero, Mario D.; d’Ischia, Marco; Gadaleta, Maria Nicola; Pallardó, Federico V.; Petrović, Sandra; Tiano, Luca; Zatterale, Adriana
An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluated for the following endpoints: (a) treated diseases; (b) dosages, number of enrolled patients and duration of treatment; (c) trial success for each MN or MN combinations as reported by authors. The reports satisfying the above endpoints included total numbers of trials and frequencies of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with “classical” antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN, suggesting forthcoming clinical studies. The criteria in study design and monitoring MN-based clinical trials are discussed. PMID:25380523
California Natural Resource Agency — The California Land Conservation Act of 1965 - commonly referred to as the Williamson Act - is the State's primary program for the conservation of private land in...
Glynne-Jones, R; Kadalayil, L; Meadows, H M; Cunningham, D; Samuel, L; Geh, J I; Lowdell, C; James, R; Beare, S; Begum, R; Ledermann, J A; Sebag-Montefiore, D
Squamous cell carcinoma of the anus (SCCA) is highly sensitive to chemoradiation (CRT) which achieves good loco-regional control and preserves anal function. However, some patients require permanent stoma formation either as a result of surgery on relapse, poor anal function or treatment-related symptoms. Our aim was to determine patient, tumour and treatment-related colostomy rates following CRT and maintenance chemotherapy in the ACT II trial. The ACT II trial recruited 940 patients comparing 5FU-based CRT using cisplatin (CisP) or mitomycin C (MMC) with or without additional maintenance chemotherapy. We investigated the association between colostomy-free survival (CFS) and progression-free survival (PFS) with age, gender, T-stage, N-stage, treatment and baseline haemoglobin. The median follow-up was 5.1 years (n = 884 evaluable/940); tumour site canal (84%), margin (14%); stage T1/T2 (52%), T3/T4 (46%); N+ (32%), N0 (62%). Twenty out of 118 (17%) colostomies fashioned before CRT were reversed within 8 months. One hundred and twelve patients had a post-treatment colostomy due to persistent disease (98) or morbidity (14). Fifty-two per cent (61/118) of all pre-treatment colostomies were never reversed. The 5-year CFS rates were 68% MMC/Maint, 70% CisP/Maint, 68% MMC/No-maint and 65% CisP/No-maint. CRT with CisP did not improve CFS when compared with MMC (hazard ratio: 1.04, 95% confidence interval: 0.82-1.31, P = 0.74). The 5-year CFS rates were higher for T1/T2 (79%) than T3/T4 (54%) tumours and higher for node-negative (72%) than node-positive (60%) patients. Significant predictors of CFS were gender, T-stage and haemoglobin, while treatment factors had no impact on outcome. Similar associations were found between PFS and tumour/treatment-related factors. The majority (52%) of pre-treatment colostomies were never reversed. Neither CRT with 5FU/CisP nor maintenance chemotherapy impacted on CFS. The low risk of colostomy for late effects (1.7%) is likely to be
Bergström, Malin; Rudman, Ann; Waldenström, Ulla; Kieler, Helle
To explore if antenatal fear of childbirth in men affects their experience of the birth event and if this experience is associated with type of childbirth preparation. Data from a randomized controlled multicenter trial on antenatal education. 15 antenatal clinics in Sweden between January 2006 and May 2007. 762 men, of whom 83 (10.9%) suffered from fear of childbirth. Of these 83 men, 39 were randomized to psychoprophylaxis childbirth preparation where men were trained to coach their partners during labor and 44 to standard care antenatal preparation for childbirth and parenthood without such training. Experience of childbirth was compared between men with and without fear of childbirth regardless of randomization, and between fearful men in the randomized groups. Analyses by logistic regression adjusted for sociodemographic variables. Self-reported data on experience of childbirth including an adapted version of the Wijma Delivery Experience Questionnaire (W-DEQ B). Men with antenatal fear of childbirth more often experienced childbirth as frightening than men without fear: adjusted odds ratio 4.68, 95% confidence interval 2.67-8.20. Men with antenatal fear in the psychoprophylaxis group rated childbirth as frightening less often than those in standard care: adjusted odds ratio 0.30, 95% confidence interval 0.10-0.95. Men who suffer from antenatal fear of childbirth are at higher risk of experiencing childbirth as frightening. Childbirth preparation including training as a coach may help fearful men to a more positive childbirth experience. Additional studies are needed to support this conclusion. © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.
... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 13-149] Privacy Act of 1974; Privacy Act... proposed revisions to existing Privacy Act systems of records. SUMMARY: Pursuant to the provisions of the Privacy Act of 1974 (5 U.S.C. 552a), the National Aeronautics and Space Administration is issuing public...
Rogers, David E.C.; Brent, Alan C.
Formal waste management services are not accessible for the majority of primary healthcare clinics on the African continent, and affordable and practicable technology solutions are required in the developing country context. In response, a protocol was established for the first quantitative and qualitative evaluation of relatively low cost small-scale incinerators for use at rural primary healthcare clinics. The protocol comprised the first phase of four, which defined the comprehensive trials of three incineration units. The trials showed that all of the units could be used to render medical waste non-infectious, and to destroy syringes or render needles unsuitable for reuse. Emission loads from the incinerators are higher than large-scale commercial incinerators, but a panel of experts considered the incinerators to be more acceptable compared to the other waste treatment and disposal options available in under-serviced rural areas. However, the incinerators must be used within a safe waste management programme that provides the necessary resources in the form of collection containers, maintenance support, acceptable energy sources, and understandable operational instructions for the incinerators, whilst minimising the exposure risks to emissions through the correct placement of the units in relation to the clinic and the surrounding communities. On-going training and awareness building are essential in order to ensure that the incinerators are correctly used as a sustainable waste treatment option
Simister, Heather D; Tkachuk, Gregg A; Shay, Barbara L; Vincent, Norah; Pear, Joseph J; Skrabek, Ryan Q
In this study, 67 participants (95% female) with fibromyalgia (FM) were randomly assigned to an online acceptance and commitment therapy (online ACT) and treatment as usual (TAU; ACT + TAU) protocol or a TAU control condition. Online ACT + TAU participants were asked to complete 7 modules over an 8-week period. Assessments were completed at pre-treatment, post-treatment, and 3-month follow-up periods and included measures of FM impact (primary outcome), depression, pain, sleep, 6-minute walk, sit to stand, pain acceptance (primary process variable), mindfulness, cognitive fusion, valued living, kinesiophobia, and pain catastrophizing. The results indicated that online ACT + TAU participants significantly improved in FM impact, relative to TAU (P online ACT + TAU were also found on measures of depression (P = .02), pain (P = .01), and kinesiophobia (P = .001). Although preliminary, this study highlights the potential for online ACT to be an efficacious, accessible, and cost-effective treatment for people with FM and other chronic pain conditions. Online ACT reduced FM impact relative to a TAU control condition in this randomized controlled trial. Reductions in FM impact were mediated by improvements in pain acceptance. Online ACT appears to be a promising intervention for FM. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.
Linda L. Langner; Peter J. Ince
The Resources Planning Act (RPA) Assessment provides a nationally consistent analysis of the status and trends of the Nation's renewable forest resources. A global scenario approach was taken for the 2010 RPA Assessment to provide a shared world view of potential futures. The RPA Assessment scenarios were linked to the global scenarios and climate projections used...
The single electron double-slit interference experiment is given a time-symmetric interpretation and visualization in terms of the intermediate amplitude of transition between the particle source and the detection point. It is seen that the retarded (causal) amplitude of the electron wave expanding from the source shows an advanced (retrocausal) bifurcation and merging in passing through the double-slit and converges towards the detection point as if guided by the advanced (retrocausal) wave from the detected electron. An experiment is proposed to confirm the causation-retrocausation symmetry of the electron behavior by observing the insensitivity of the interference pattern to non-magnetic obstacles placed in the shadows of the retarded and advanced waves appearing on the rear and front sides of the double-slit.
Fiehler, Jens [University Medical Centre Hamburg-Eppendorf, Department of Neuroradiology, Hamburg (Germany); Soederman, Michael [Karolinska University Hospital, Department of Neuroradiology, Stockholm (Sweden); Turjman, Francis [Hopital neurologique, Centre de Neurosciences Cognitives, Department of Neuroradiology, Lyon (France); White, Philip M. [University of Edinburgh, Department of Clinical Neurosciences, Western General Hospital, Edinburgh (United Kingdom); Bakke, Soeren Jacob [Oslo University Hospital, Department of Neuroradiology, Oslo (Norway); Mangiafico, Salvatore [University Hospital Careggi, Interventional Neuroradiology Unit, Florence (Italy); Kummer, Ruediger von [University of Dresden, Department of Neuroradiology, Dresden (Germany); Muto, Mario [University of Naples, Department of Neuroradiology, Naples (Italy); Cognard, Christophe [Hopital Purpan, Service de Neuroradiologie, Toulouse (France); Gralla, Jan [Inselspital Bern, Department of Neuroradiology, Bern (Switzerland)
Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines. (orig.)
Fiehler, Jens; Söderman, Michael; Turjman, Francis; White, Philip M; Bakke, Søren Jacob; Mangiafico, Salvatore; von Kummer, Rüdiger; Muto, Mario; Cognard, Christophe; Gralla, Jan
Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.
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... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 12-100] Privacy Act of 1974; Privacy Act... proposed revisions to an existing Privacy Act system of records. SUMMARY: Pursuant to the provisions of the Privacy Act of 1974 (5 U.S.C. 552a), the National Aeronautics and Space Administration is issuing public...
National Aeronautics and Space Administration — The Inflationary Model of the universe has provided a theoretical platform for modern observational experiments in the field of cosmology. A well-defined method of...
Full Text Available Whilst there appears to be no ergogenic effect from inhaled salbutamol no study has investigated the impact of the acute inhalation of 1600 µg, the World Anti-Doping Agency (WADA daily upper limit, on endurance running performance. To investigate the ergogenic effect of an acute inhalation of short acting β2-agonists at doses up to 1600 µg on 5 km time trial performance and resultant urine concentration. Seven male non-asthmatic runners (mean ± SD; age 22.4 ± 4.3 years; height 1.80 ± 0.07 m; body mass 76.6 ± 8.6 kg provided written informed consent. Participants completed six 5 km time-trials on separate days (three at 18 °C and three at 30 °C. Fifteen minutes prior to the initiation of each 5 km time-trial participants inhaled: placebo (PLA, 800 µg salbutamol (SAL800 or 1600 µg salbutamol (SAL1600. During each 5 km time-trial HR, VO2, VCO2, VE, RPE and blood lactate were measured. Urine samples (90 ml were collected between 30-180 minutes post 5 km time-trial and analysed for salbutamol concentration. There was no significant difference in total 5 km time between treatments (PLA 1714.7 ± 186.2 s; SAL800 1683.3 ± 179.7 s; SAL1600 1683.6 ± 190.7 s. Post 5 km time-trial salbutamol urine concentration between SAL800 (122.96 ± 69.22 ug·ml-1 and SAL1600 (574.06 ± 448.17 ug·ml-1 were not significantly different. There was no improvement in 5 km time-trial performance following the inhalation of up to 1600 µg of salbutamol in non-asthmatic athletes. This would suggest that the current WADA guidelines, which allow athletes to inhale up to 1600 µg per day, is sufficient to avoid pharmaceutical induced performance enhancement.
Dismantling techniques for plutonium-contaminated gloveboxes: experience from first year of decommissioning; Zerlegungstechniken fuer Pu-kontaminierte Handschuhkaesten: Erfahrungsbericht nach einem Jahr Rueckbau
Baumann, R.; Faber, P. [Siemens Power Generation, Decommissioning Projects, Hanau (Germany)
At the mixed-oxide (MOX) processing facility formerly operated by ALKEM GmbH in Hanau, Germany - which was taken over to Siemens in 1988 and renamed Siemens' Hanau Fuel Fabrication Plant, MOX facility - around 8500 kg of plutonium were processed to make MOX fuel rods and fuel assemblies since production started in 1965. After shutdown of the facility by the authorities in mid-1991 for political reasons, the remaining nuclear fuel materials were processed during the subsequent ''cleanout'' phase starting in 1997 into rods and assemblies suitable for long-term storage. The last step in cleanout consisted of ''flushing'' the production equipment with depleted uranium and thoroughly cleaning the gloveboxes. During cleanout around 700 kg of plutonium were processed in the form of mixed oxides. The cleanout phase including the subsequent cleaning and flushing operations ended on schedule in September 2001 without any significant problems. Starting in mid-1999, the various glovebox dismantling techniques were tested using uncontaminated components while cleanout was still in progress and then, once these trials had been successfully completed, further qualified through use on actual components. The pilot-phase trials required four separate licenses under Section 7, Subsection (3) of the German Atomic Energy Act. Thanks to detailed advance planning and experience from the pilot trials the individual dismantling steps could be described in sufficient detail for the highly complex German licensing procedure. The first partial license for decommissioning the MOX facility under Sec. 7, Subsec. (3) of the Atomic Energy Act was issued on May 28, 2001. It mainly covers dismantling of the interior equipment inside the gloveboxes a well as the gloveboxes themselves. Actual decommissioning work inside the former production areas of the MOX facility started on a large scale in early September 2001. (orig.)
Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, or ... humans. What Are Clinical Trials? Clinical trials are research studies that explore whether a medical strategy, treatment, or ...
On January 14, 2009, the German federal government introduced into parliament the 10th Act Amending the Atomic Energy Act. In the first reading in the federal parliament, Federal Minister for the Environment Gabriel emphasized 2 main points: Intensified protection of nuclear facilities and of transports of radioactive substances against unauthorized interventions; transfer by law to the Federal Office for Radiological Protection (BfS) of decommissioning of the Asse mine. Reliability review: The amendment to Sec.12 b of the Atomic Energy Act is to meet the different safety and security conditions after the terrorist attacks on September 11, 2001 in the United States and other terrorist activities afterwards (London, Madrid) also with respect to hazards arising to nuclear facilities and nuclear transports. The bill must be seen in conjunction with the Ordinance on Reliability Reviews under the Atomic Energy Act dated July 1, 1999 which covers reviews of reliability of persons holding special responsibilities. Asse II mine: The competence of the Federal Office for Radiological Protection is achieved by an amendment to Sec.23, Para.1, Number 2, Atomic Energy Act, in which the words ''and for the Asse II mine'' are added after the word ''waste.'' Further proceedings depend on the additional provision in a new Sec.57 b, Atomic Energy Act. Accordingly, the operation and decommissioning of the Asse II mine are subject to the regulations applicable to facilities of the federation pursuant to Sec.9a, Para.3. In this way, Asse II is given the same legal status as the federal waste management facilities. Moreover, it is stipulated that the mine is to be shut down immediately. (orig.)
Morrison, Zoe; Douglas, Anne; Bhopal, Raj; Sheikh, Aziz
To explore the reasons for enrolling, experiences of participating and reasons for remaining in a family-based, cluster randomised controlled trial of a dietitian-delivered lifestyle modification intervention aiming to reduce obesity in South Asians at high risk of developing diabetes. Qualitative study using narrative interviews of a purposive sample of trial participants following completion of the intervention. Data were thematically analysed. The intervention was conducted in Scotland and resulted in a modest decrease in weight, but did not statistically reduce the incidence of diabetes. We conducted 21 narrative interviews with 24 participants (20 trial participants and four family volunteers). Many participants were motivated to participate because of: known family history of diabetes and the desire to better understand diabetes-related risks to their own and their family's health; ways to mitigate these risks and to benefit from personalised monitoring. Home-based interventions, communication in the participant's chosen language(s) and continuity in dietitians supported their continuing engagement with the trial. Adaptations in food choices were initially accommodated by participants, although social and faith-based responsibilities were reported as important barriers to persevering with agreed dietary goals. Many participants reported that increasing their level of physical activity was difficult given their long working hours, physically demanding employment and domestic commitments; this being compounded by Scotland's challenging climate and a related reluctance to exercise in the outdoors. Although participants had strong personal interests in participation and found the information provided by dietitians useful, they nonetheless struggled to incorporate the dietary and exercise recommendations into their daily lives. In particular, increasing levels of physical exercise was described as an additional and in some cases unachievable burden. Consideration
Article 21 is replaced by articles 21 to 21b. According to this, fees or reimbursements for expenses for official acts (e.g. decisions, supervisory acts, safeguarding of nuclear fuels) as well as for the use of facilities according to article 9a, section 3, of the Atomic Energy Act (e.g. Laender facilities to collect nuclear waste). (HP) [de
Full Text Available This paper explores the role that societal culture may play in terms of acting as an inhibitor or enabler when creating conditions conducive to innovative enterprise. To further understanding of this concept, the paper's authors explore different cultural influences and traditions of the country of Germany and the Canadian province of Ontario against the backdrop of the introduction of a government green energy policy and how local business reacts to new opportunities forthcoming from this shift in policy direction. The authors contend that the current Ontario psyche has contributed to an overall cultural drag on innovative activities. They demonstrate that in no place is this cultural impact more evident than the apparent lack of home-grown innovative activity surrounding green energy entrepreneurship; where, in spite of progressive and favourable provincial government policy, continued manufacturing growth is led by offshore companies The Ontario experience is in sharp contrast to current and historical German activity, when it comes to local innovation and advances in green energy. While Germany officially enacted their green energy act at the turn of the last century, experts agree that the German tenure with going green is in fact 35 to 40 years in the making. Although it has been contended that unique historical conditions such as postwar reconstruction and the reunification of the former East and West Germany have been significant contributing factors to Germany's embracing of sustainable energy, the authors of this paper contend that cultural factors such as the German sense of naturfreund; an overwhelming sense of being a nature-lover, may also play a significant role. In their exploration the authors build upon Hofstede's cultural dimension theory unpacking specific cultural components, as they compare actions and responses made by German and Ontarian policy-makers and business decision-makers.
... Section 40.16 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY PRIVACY OF... Reporting Act. Nothing in this part shall be construed to modify, limit, or supersede the operation of the... provisions of this part regarding whether information is transaction or experience information under section...
Gordon, Michael S; Vocci, Frank J; Fitzgerald, Terrence T; O'Grady, Kevin E; O'Brien, Charles P
Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases has been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. We describe the background and rationale for the study, its aims, hypotheses, and study design. The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. ClinicalTrials.gov: NCT02867124. Copyright © 2016 Elsevier Inc. All rights reserved.
A walking programme and a supervised exercise class versus usual physiotherapy for chronic low back pain: a single-blinded randomised controlled trial. (The Supervised Walking In comparison to Fitness Training for Back Pain (SWIFT) Trial).
Hurley, Deirdre A
BACKGROUND: Chronic low back pain (CLBP) is a persistent disabling condition with rising significant healthcare, social and economic costs. Current research supports the use of exercise-based treatment approaches that encourage people with CLBP to assume a physically active role in their recovery. While international clinical guidelines and systematic reviews for CLBP support supervised group exercise as an attractive first-line option for treating large numbers of CLBP patients at low cost, barriers to their delivery include space and time restrictions in healthcare settings and poor patient attendance. The European Clinical Guidelines have identified the need for research in the use of brief\\/minimal contact self-activation interventions that encourage participation in physical activity for CLBP. Walking may be an ideally suited form of individualized exercise prescription as it is easy to do, requires no special skills or facilities, and is achievable by virtually all ages with little risk of injury, but its effectiveness for LBP is unproven. METHODS AND DESIGN: This study will be an assessor-blinded randomized controlled trial that will investigate the difference in clinical effectiveness and costs of an individualized walking programme and a supervised general exercise programme compared to usual physiotherapy, which will act as the control group, in people with chronic low back pain. A sample of 246 patients will be recruited in Dublin, Ireland through acute general hospital outpatient physiotherapy departments that provide treatment for people with CLBP. Patients will be randomly allocated to one of the three groups in a concealed manner. The main outcomes will be functional disability, pain, quality of life, fear avoidance, back beliefs, physical activity, satisfaction and costs, which will be evaluated at baseline, and 3, 6 and 12 months [follow-up by pre-paid postage]. Qualitative telephone interviews and focus groups will be embedded in the research
Full Text Available Human morality entails a typical self-control dilemma in which one must conform to moral rules or socially desirable norms while exerting control over amoral, selfish impulses. Extant research regarding the connection between self-control and level of construal suggest that, compared with a low-level, concrete construal (highlighting means and resources, e.g., answering ‘how’ questions, a high-level, abstract construal (highlighting central goals, e.g., answering ‘why’ questions promotes self-control. Hence, construing morality at higher levels rather than lower levels should engender greater self-control and, it follows, promote a tendency to perform moral acts. We conducted two experiments to show that answering “why” (high-level construal vs. “how” (low-level construal questions regarding morality was associated with a situational state of greater self-control, as indexed by less Stroop interference in the Stroop color-naming task (Experiments 1 and 2. Participants exposed to “why” questions regarding morality displayed a greater inclination for volunteerism (Experiment 1, showed a lower tendency toward selfishness in a dictator game (Experiment 2, and were more likely to return undeserved money (Experiment 2 compared with participants exposed to “how” questions regarding morality. In both experiments, self-control mediated the effect of a high-level construal of morality on dependent measures. The current research constitutes a new approach to promoting prosociality and moral education. Reminding people to think abstractly about human morality may help them to generate better control over the temptation to benefit from unethical acts and make it more likely that they will act morally.
Wu, Chia-Chun; Wu, Wen-Hsiung; Chiou, Wen-Bin
Human morality entails a typical self-control dilemma in which one must conform to moral rules or socially desirable norms while exerting control over amoral, selfish impulses. Extant research regarding the connection between self-control and level of construal suggest that, compared with a low-level, concrete construal (highlighting means and resources, e.g., answering 'how' questions), a high-level, abstract construal (highlighting central goals, e.g., answering 'why' questions) promotes self-control. Hence, construing morality at higher levels rather than lower levels should engender greater self-control and, it follows, promote a tendency to perform moral acts. We conducted two experiments to show that answering "why" (high-level construal) vs. "how" (low-level construal) questions regarding morality was associated with a situational state of greater self-control, as indexed by less Stroop interference in the Stroop color-naming task (Experiments 1 and 2). Participants exposed to "why" questions regarding morality displayed a greater inclination for volunteerism (Experiment 1), showed a lower tendency toward selfishness in a dictator game (Experiment 2), and were more likely to return undeserved money (Experiment 2) compared with participants exposed to "how" questions regarding morality. In both experiments, self-control mediated the effect of a high-level construal of morality on dependent measures. The current research constitutes a new approach to promoting prosociality and moral education. Reminding people to think abstractly about human morality may help them to generate better control over the temptation to benefit from unethical acts and make it more likely that they will act morally.
Ogutu, Bernhards R; Baiden, Rita; Diallo, Diadier; Smith, Peter G; Binka, Fred N
The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that
Fleming, Padhraig S; Lynch, Christopher D; Pandis, Nikolaos
Clinical trials are used to appraise the effectiveness of clinical interventions throughout medicine and dentistry. Randomized controlled trials (RCTs) are established as the optimal primary design and are published with increasing frequency within the biomedical sciences, including dentistry. This review outlines common pitfalls associated with the conduct of randomized controlled trials in dentistry. Common failings in RCT design leading to various types of bias including selection, performance, detection and attrition bias are discussed in this review. Moreover, methods of minimizing and eliminating bias are presented to ensure that maximal benefit is derived from RCTs within dentistry. Well-designed RCTs have both upstream and downstream uses acting as a template for development and populating systematic reviews to permit more precise estimates of treatment efficacy and effectiveness. However, there is increasing awareness of waste in clinical research, whereby resource-intensive studies fail to provide a commensurate level of scientific evidence. Waste may stem either from inappropriate design or from inadequate reporting of RCTs; the importance of robust conduct of RCTs within dentistry is clear. Optimal reporting of randomized controlled trials within dentistry is necessary to ensure that trials are reliable and valid. Common shortcomings leading to important forms or bias are discussed and approaches to minimizing these issues are outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.
Roos, Daniel E.; Davis, Sidney R.; Turner, Sandra L.; O'Brien, Peter C.; Spry, Nigel A.; Burmeister, Bryan H.; Hoskin, Peter J.; Ball, David L.
Background and purpose: Trans-Tasman Radiation Oncology Group 96.05 is a prospective randomized controlled trial comparing a single 8 Gy with 20 Gy in five fractions of radiotherapy (RT) for neuropathic pain due to bone metastases. This paper summarizes the quality assurance (QA) activities for the first 234 patients (accrual target 270). Materials and methods: Independent audits to assess compliance with eligibility/exclusion criteria and appropriateness of treatment of the index site were conducted after each cohort of approximately 45 consecutive patients. Reported serious adverse events (SAEs) in the form of cord/cauda equina compression or pathological fracture developing at the index site were investigated and presented in batches to the Independent Data Monitoring Committee. Finally, source data verification of the RT prescription page and treatment records was undertaken for each of the first 234 patients to assess compliance with the protocol. Results: Only one patient was found conclusively not to have genuine neuropathic pain, and there were no detected 'geographical misses' with RT fields. The overall rate of detected infringements for other eligibility criteria over five audits (225 patients) was 8% with a dramatic improvement after the first audit. There has at no stage been a statistically significant difference in SAEs by randomization arm. There was a 22% rate of RT protocol variations involving ten of the 14 contributing centres, although the rate of major dose violations (more than ±10% from protocol dose) was only 6% with no statistically significant difference by randomization arm (P=0.44). Conclusions: QA auditing is an essential but time-consuming component of RT trials, including those assessing palliative endpoints. Our experience confirms that all aspects should commence soon after study activation
Full Text Available The unsafe acts of workers are considered as major contributors of work-related accidents and injuries on construction sites. However, not much work has been done to address the reasons why unsafe acts of workers occur particularly in construction industry. The aim of this paper therefore, is to investigate the major unsafe acts (i.e., at-risk behavior, and the decision-to-err factors causing unsafe acts. A questionnaire survey was conducted to collect data from a total of 214 workers from 20 building construction projects in Thailand. The findings revealed that the failure of workers to wear personal protective equipment (PPE, improper lifting or handling of materials, and keeping sharp objects in dangerous locations, are the major unsafe acts which frequently occur on construction sites in Thailand. In addition, the paper reported that the top three most frequent unsafe acts are statistically associated with several decision-to-err factors, including lack of management support, management pressure, group norms, overconfidence, being uncomfortable, past experience and laziness.
White, Rebekah C; Davies, Martin; Aimola Davies, Anne M
When attention is otherwise engaged, observers may experience inattentional blindness, failing to notice objects or events that are presented in plain sight. In an inattentional blindness experiment, an unexpectedstimulus ispresented alongside primary-task stimuli, and its detection is probed. We evaluate a criterion that is commonly used to exclude observers from the data analysis. On the final experimental trial, observers do not perform the primary task, but instead look for anything new. Observers who fail to report the unexpected stimulus on thisfull-attention trialare excluded. On the basis of 4 hypothetical experiments and a review of 128 actual experiments from the literature, we demonstrate some potentially problematic consequences of implementing the full-attention-trial exclusion criterion. Excluded observers may cluster in experimental conditions and the exclusion criterion may lead researchers to understate the pervasiveness of inattentional blindness. It may even render usblindto inattentional blindness on the full-attention trial. Copyright © 2017 Elsevier Inc. All rights reserved.
Milani, Alessandra; Mazzocco, Ketti; Stucchi, Sara; Magon, Giorgio; Pravettoni, Gabriella; Passoni, Claudia; Ciccarelli, Chiara; Tonali, Alessandra; Profeta, Teresa; Saiani, Luisa
Few resources are available to quantify clinical trial-associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014. Average times spent by nurses for each activity were calculated. The "Nursing Time Required by Clinical Trial-Assessment Tool" was created as an electronic sheet that combines the average times per specified activities and mathematic functions to return the total estimated time required by a research nurse for each specific trial. The tool was tested retrospectively on 141 clinical trials. The increasing complexity of clinical research requires structured approaches to determine workforce requirements. This study provides a tool to describe the activities of a clinical trials nurse and to estimate the associated time required to deliver individual trials. The application of the proposed tool in clinical research practice could provide a consistent structure for clinical trials nursing workload estimation internationally. © 2016 John Wiley & Sons Australia, Ltd.
Cook Jonathan A
Full Text Available Abstract Background Randomised trials evaluation of surgical interventions are often designed and analysed as if the outcome of individual patients is independent of the surgeon providing the intervention. There is reason to expect outcomes for patients treated by the same surgeon tend to be more similar than those under the care of another surgeon due to previous experience, individual practice, training, and infrastructure. Such a phenomenon is referred to as the clustering effect and potentially impacts on the design and analysis adopted and thereby the required sample size. The aim of this work was to inform trial design by quantifying clustering effects (at both centre and surgeon level for various outcomes using a database of surgical trials. Methods Intracluster correlation coefficients (ICCs were calculated for outcomes from a set of 10 multicentre surgical trials for a range of outcomes and different time points for clustering at both the centre and surgeon level. Results ICCs were calculated for 198 outcomes across the 10 trials at both centre and surgeon cluster levels. The number of cases varied from 138 to 1370 across the trials. The median (range average cluster size was 32 (9 to 51 and 6 (3 to 30 for centre and surgeon levels respectively. ICC estimates varied substantially between outcome type though uncertainty around individual ICC estimates was substantial, which was reflected in generally wide confidence intervals. Conclusions This database of surgical trials provides trialists with valuable information on how to design surgical trials. Our data suggests clustering of outcome is more of an issue than has been previously acknowledged. We anticipate that over time the addition of ICCs from further surgical trial datasets to our database will further inform the design of surgical trials.
Green, Debra H.
The applicability of legal principles governing equal pay and sex discrimination in university settings is discussed. The most objective mechanism that a university can utilize to achieve compliance with the Equal Pay Act would be implementation of a salary system that relies on experience, formal education, and time in grade. (MLW)
Chochinov, Harvey Max; Kristjanson, Linda J.; Breitbart, William; McClement, Susan; Hack, Thomas F; Hassard, Tom; Harlos, Mike
Objectives Dignity Therapy is a unique, individualized, brief psychotherapy, developed for patients (and their families) living with life threatening or life limiting illness. The purpose of this study was to determine if Dignity Therapy could mitigate distress and/or bolster end-of-life experience for patients nearing death. Trial Design Multi-site randomized controlled trial, with patients assigned to Dignity Therapy, Client Centred Care or Standard Palliative Care. Study arm assignment was based on a computer-generated table of random numbers. Blinding was achieved using opaque sealed envelopes, containing allocations that were only opened once consent had been obtained. Participants Patients receiving hospital or community (hospice or home) based palliative care, in Winnipeg, New York, or Perth, randomly assigned to, Dignity Therapy [n=108], Client Centered Care [n=107] and Standard Palliative Care (n=111). Main Outcome Measures The primary outcome measures included the FACIT Spiritual Well-Being Scale, the Patient Dignity Inventory, the Hospital Anxiety and Depression Scale; items from the Structured Interview for Symptoms and Concerns, the Quality of Life Scale and a modified Edmonton Symptom Assessment Scale. Mean changes between baseline and end of intervention ratings were determined. Secondary outcomes, examining self-report end-of-life experience, consisted of a post-study survey administered across all study arms. Intervention Dignity Therapy, a novel, brief psychotherapy, provides patients with life threatening and life limiting illnesses an opportunity to speak about things that matter most to them. These recorded conversations form the basis of a generativity document, which patients can bequeath to individuals of their choosing. Client Centred Care is a supportive psychotherapeutic approach, in which research nurse/therapists guide patients through discussions focusing on here and now issues. Findings No significant differences across study arms
Toye, Francine; Williamson, Esther; Williams, Mark A; Fairbank, Jeremy; Lamb, Sarah E
Using an example of qualitative research embedded in a non-surgical feasibility trial, we explore the benefits of including qualitative research in trial design and reflect on epistemological challenges. We interviewed 18 trial participants and used methods of Interpretive Phenomenological Analysis. Our findings demonstrate that qualitative research can make a valuable contribution by allowing trial stakeholders to see things from alternative perspectives. Specifically, it can help to make specific recommendations for improved trial design, generate questions which contextualize findings, and also explore disease experience beyond the trial. To make the most out of qualitative research embedded in quantitative design it would be useful to (a) agree specific qualitative study aims that underpin research design, (b) understand the impact of differences in epistemological truth claims, (c) provide clear thematic interpretations for trial researchers to utilize, and (d) include qualitative findings that explore experience beyond the trial setting within the impact plan. © The Author(s) 2016.
Keysar, Boaz; Converse, Benjamin A; Wang, Jiunwen; Epley, Nicholas
Unlike economic exchange, social exchange has no well-defined "value." It is based on the norm of reciprocity, in which giving and taking are to be repaid in equivalent measure. Although giving and taking are colloquially assumed to be equivalent actions, we demonstrate that they produce different patterns of reciprocity. In five experiments utilizing a dictator game, people reciprocated in like measure to apparently prosocial acts of giving, but reciprocated more selfishly to apparently antisocial acts of taking, even when the objective outcomes of the acts of giving and taking were identical. Additional results demonstrate that acts of giving in social exchanges are perceived as more generous than objectively identical acts of taking, that taking tends to escalate, and that the asymmetry in reciprocity is not due to gaining versus losing resources. Reciprocity appears to operate on an exchange rate that assigns value to the meaning of events, in a fashion that encourages prosocial exchanges.
Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.
Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255
Full Text Available Three recently published trials, MR RESCUE, IMS III, and SYNTHESIS Expansion, evaluating the efficacy and safety of endovascular treatment of acute ischemic stroke have generated concerns about the future of endovascular approach. However, the tremendous evolution that imaging and endovascular treatment modalities have undergone over the past several years has raised doubts about the validity of these trials. In this paper, we review the role of endovascular treatment strategies in acute ischemic stroke and discuss the limitations and shortcomings that prevent generalization of the findings of recent trials. We also provide our experience in endovascular treatment of acute ischemic stroke.
Full Text Available Adoptive Cell Transfer (ACT of Tumor-Infiltrating Lymphocytes (TIL in combination with lymphodepletion has proven to be an effective treatment for metastatic melanoma patients, with an objective response rate in 50%–70% of the patients. It is based on the ex vivo expansion and activation of tumor-specific T lymphocytes extracted from the tumor and their administration back to the patient. Various TIL-ACT trials, which differ in their TIL generation procedures and patient preconditioning, have been reported. In the latest clinical studies, genetically engineered peripheral T cells were utilized instead of TIL. Further improvement of adoptive T cell transfer depends on new investigations which seek higher TIL quality, increased durable response rates, and aim to treat more patients. Simplifying this therapy may encourage cancer centers worldwide to adopt this promising technology. This paper focuses on the latest progress regarding adoptive T cell transfer, comparing the currently available protocols and discussing their advantages, disadvantages, and implication in the future.
Staubach, P; Metz, M; Chapman-Rothe, N; Sieder, C; Bräutigam, M; Canvin, J; Maurer, M
Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). Of the 91 patients randomized to omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57-63 days with omalizumab and Omalizumab significantly improved angioedema-specific QoL (P omalizumab. Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M
To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track
A set of legislation consisting of three Acts in the field of radiation protection and nuclear safety was passed by both Houses of Parliament on 10 December 1998 and was proclaimed on 5 February 1999. Act No. 133 - Australian Radiation Protection and Nuclear Safety Act, which is a framework Law, established the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) as the regulatory body for radiation protection and nuclear safety, in place of the Nuclear Safety Bureau. The Chief Executive Officer of ARPANSA, who is appointed by the Governor-General for a term of up to 5 years, is obliged to submit annual and quarterly reports to the Minister on the operations of the Chief Executive Officer, ARPANSA, the Council, the Radiation Health Committee and the Nuclear Safety Committee. The Council is a consultative body which examines issues relating to radiation protection and nuclear safety and advises the Chief Executive Officer on these issues as well as on the adoption of recommendations, policies and codes. The Radiation Health Committee and the Nuclear Safety Committee are to be established as advisory committees to the Chief Executive Officer or the Council. Both committees should draft national policies, codes and standards in their respective fields and review their effectiveness periodically. The second in this series of legislation, Act No. 134, Australian Radiation Protection and Nuclear Safety (License Charges) Act requires holders of both facility and source licenses to pay an annual charge, to be prescribed by the regulations. The third, Act No. 135 , Australian Radiation Protection and Nuclear Safety (Consequential Amendments) Act repeals those provisions of the 1987 Australian Nuclear Science and Technology Organisation Act which concern the Nuclear Safety Bureau, and the 1978 Environment Protection Act as a whole
A set of legislation consisting of three Acts in the field of radiation protection and nuclear safety was passed by both Houses of Parliament on 10 December 1998 and was proclaimed on 5 February 1999. Act No. 133 - Australian Radiation Protection and Nuclear Safety Act, which is a framework Law, established the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) as the regulatory body for radiation protection and nuclear safety, in place of the Nuclear Safety Bureau. The Chief Executive Officer of ARPANSA, who is appointed by the Governor-General for a term of up to 5 years, is obliged to submit annual and quarterly reports to the Minister on the operations of the Chief Executive Officer, ARPANSA, the Council, the Radiation Health Committee and the Nuclear Safety Committee. The Council is a consultative body which examines issues relating to radiation protection and nuclear safety and advises the Chief Executive Officer on these issues as well as on the adoption of recommendations, policies and codes. The Radiation Health Committee and the Nuclear Safety Committee are to be established as advisory committees to the Chief Executive Officer or the Council. Both committees should draft national policies, codes and standards in their respective fields and review their effectiveness periodically. The second in this series of legislation, Act No. 134, Australian Radiation Protection and Nuclear Safety (License Charges) Act requires holders of both facility and source licenses to pay an annual charge, to be prescribed by the regulations. The third, Act No. 135 , Australian Radiation Protection and Nuclear Safety (Consequential Amendments) Act repeals those provisions of the 1987 Australian Nuclear Science and Technology Organisation Act which concern the Nuclear Safety Bureau, and the 1978 Environment Protection Act as a whole
Rasmussen, Ole Dahl; Malchow-Møller, Nikolaj; Andersen, Thomas Barnebeck
Recent advances in the use of randomised control trials to evaluate the effect of development interventions promise to enhance our knowledge of what works and why. A core argument supporting randomised studies is the claim that they have high internal validity. The authors argue that this claim...... is weak as long as a trial registry of development interventions is not in place. Without a trial registry, the possibilities for data mining, created by analyses of multiple outcomes and subgroups, undermine internal validity. Drawing on experience from evidence-based medicine and recent examples from...
Recent experiments (Giustina et al 2013 Nature 497 227–30; Christensen et al 2013 Phys. Rev. Lett. 111 130406) have reached detection efficiencies sufficient to close the detection loophole, testing the Clauser–Horne version of Bell's inequality. For a similar future experiment to be completely loophole-free, it will be important to have discrete experimental trials with randomized measurement settings for each trial, and the statistical analysis should not overlook the possibility of a local state varying over time with possible dependence on earlier trials (the ‘memory loophole’). In this paper, a mathematical model for such an experiment is presented, and a method for statistical analysis that is robust to memory effects is introduced. Additionally, a new method for calculating exact p-values for martingale-based statistics is described; previously, only non-sharp upper bounds derived from the Azuma–Hoeffding inequality have been available for such statistics. This improvement decreases the required number of experimental trials to demonstrate non-locality. The statistical techniques are applied to the data of Giustina et al (2013 Nature 497 227–30) and Christensen et al (2013 Phys. Rev. Lett. 111 130406) and found to perform well. (paper)
Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials.
Majer, Istvan M; Gaughran, Fiona; Sapin, Christophe; Beillat, Maud; Treur, Maarten
Treatment with long-acting injectable (LAI) antipsychotic medication is an important element of relapse prevention in schizophrenia. Recently, the intramuscular once-monthly formulation of aripiprazole received marketing approval in Europe and the United States for schizophrenia. This study aimed to compare aripiprazole once-monthly with other LAI antipsychotics in terms of efficacy, tolerability, and safety. A systematic literature review was conducted to identify relevant double-blind randomized clinical trials of LAIs conducted in the maintenance treatment of schizophrenia. MEDLINE, MEDLINE In-Process, Embase, the Cochrane Library, PsycINFO, conference proceedings, clinical trial registries, and the reference lists of key review articles were searched. The literature search covered studies dating from January 2002 to May 2013. Studies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo. Data extracted included study details, study duration, the total number of patients in each treatment arm, efficacy, tolerability, and safety outcomes. The efficacy outcome contained the number of patients that experienced a relapse, tolerability outcomes included the number of patients that discontinued treatment due to treatment-related adverse events (AEs), and that discontinued treatment due to reasons other than AEs (e.g., loss to follow-up). Safety outcomes included the incidence of clinically relevant weight gain and extrapyramidal symptoms. Data were analyzed by applying a mixed treatment comparison competing risks model (efficacy) and using binary models (safety). There was no statistically significant
Christiansen, Jens Sandahl; Backeljauw, Philippe F; Bidlingmaier, Martin
OBJECTIVE: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). PARTICIPANTS: A closed meeting of 55 international scientists with expertise in GH, including...... and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final...
... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (11-091)] Privacy Act of 1974; Privacy Act...: Revisions of NASA Appendices to Privacy Act System of Records. SUMMARY: Notice is hereby given that NASA is... Privacy Act of 1974. This notice publishes those amendments as set forth below under the caption...
Chen, Keliang; Lu, Pei; Song, Rijin; Zhang, Jiexiu; Tao, Rongzhen; Wang, Zijie; Zhang, Wei; Gu, Min
Abstract Background: The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Results: Six studi...
... 7 Agriculture 3 2010-01-01 2010-01-01 false Act. 65.100 Section 65.100 Agriculture Regulations of... MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) COUNTRY OF ORIGIN LABELING OF BEEF..., AND GINSENG General Provisions Definitions § 65.100 Act. Act means the Agricultural Marketing Act of...
Full Text Available ... take part in a clinical trial. When researchers think that a trial's potential risks are greater than ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...
Full Text Available ... to-kol). This plan explains how the trial will work. The trial is led by a principal ... for the clinical trial. The protocol outlines what will be done during the clinical trial and why. ...
Full Text Available ... questions and clinical trials. Optimizing our Clinical Trials Enterprise NHLBI has a strong tradition of supporting clinical ... multi-pronged approach to Optimize our Clinical Trials Enterprise that will make our clinical trials enterprise even ...
Full Text Available ... of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are ... earlier than they would be in general medical practice. This is because late-phase trials have large ...
Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...
Full Text Available ... clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a ... will be done during the clinical trial and why. Each medical center that does the study uses ...
Full Text Available ... medical strategy, treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ...
Australian Science Education Project, Toorak, Victoria.
This is a National Trial Print of a unit on petroleum developed for the Australian Science Education Project. The package contains the teacher's edition of the written material and a script for a film entitled "The Extraordinary Experience of Nicholas Nodwell" emphasizing the uses of petroleum and petroleum products in daily life and…
Darbyshire, Julie Lorraine; Price, Hermione Clare
To identify the most appropriate format for results dissemination to maximise understanding of trial results. Qualitative. Of the original 58 4-T trial centres, 34 agreed to take part in this ancillary research. All participants from these centres were eligible. All 343 participants were sent questionnaires. The low response rate meant that we were unable to make any firm conclusions about the patients' preferred method of dissemination; however, we were able to comment on the level of understanding demonstrated by the trial participants. All 40 (12%) returned questionnaires were received from 15 centres. We received no questionnaires from over half of the centres. The questionnaires which were returned demonstrated broad satisfaction with the results letter, general enthusiasm for the trial and a variable level of understanding of the results; however, there was a high proportion of responders who were not clear on why the research was undertaken or what the results meant. The low response rate may be related to delays during the trial set-up process suggesting that interest in a study quickly wanes for both patients and centres. From this we deduce that rapid dissemination of results is needed if it is to have any impact at all. The responders are likely to reflect a biased cohort who were both enthusiastic about the research and who had a good experience during their 3 years in the 4-T trial. It is perhaps not surprising therefore that the overview is positive. That this population was still not fully informed about the purpose of the research would seem to confirm a low level of understanding among the general public which we suggest should be addressed during the consent process.
Gawler, S; Skelton, D A; Dinan-Young, S; Masud, T; Morris, R W; Griffin, M; Kendrick, D; Iliffe, S
Falls are common in the older UK population and associated costs to the NHS are high. Systematic reviews suggest that home exercise and group-based exercise interventions, which focus on progressively challenging balance and increasing strength, can reduce up to 42% of falls in those with a history of falls. The evidence is less clear for those older adults who are currently at low risk of falls. ProAct65+, a large, cluster-randomised, controlled trial, investigated the effectiveness of a home exercise programme (Otago Exercise Programme (OEP)) and a group-based exercise programme (Falls Management Exercise (FaME)) compared to usual care (UC) at increasing moderate to vigorous physical activity (MVPA). This paper examines the trial's secondary outcomes; the effectiveness of the interventions at reducing falls and falls-related injuries. 1256 community-dwelling older adults (aged 65+) were recruited through GP practices in two sites (London and Nottingham). Frequent fallers (≥3 falls in last year) and those with unstable medical conditions were excluded, as were those already reaching the UK Government recommended levels of physical activity (PA) for health. Baseline assessment (including assessment of health, function and previous falls) occurred before randomisation; the intervention period lasted 24 weeks and there was an immediate post-intervention assessment; participants were followed up every six months for 24 months. Falls data were analysed using negative binomial modelling. Falls data were collected prospectively during the intervention period by 4-weekly diaries (6 in total). Falls recall was recorded at the 3-monthly follow-ups for a total of 24 months. Balance was measured at baseline and at the end of the intervention period using the Timed Up & Go and Functional Reach tests. Balance confidence (CONFbal), falls risk (FRAT) and falls self-efficacy (FES-I) were measured by questionnaire at baseline and at all subsequent assessment points. 294
Chaumet-Riffaud, P.; Cachin, F.; Couturier, O.; Desruet, M.D.; Kraeber-Bodere, F.; Talbot, J.N.; Vuillez, J.P.
The particular status of radiopharmaceuticals, together with the positioning of nuclear medicine in multidisciplinary approach of oncology, lead to real difficulties for conception, validation and granting of clinical trials which are necessary for demonstrating clinical interest of new compounds, for diagnosis as well as for therapeutic use. This article is a presentation of some recent clinical trials conducted in nuclear medicine in France, showing its dynamism but also pointing out some encountered difficulties. These experiences could lead to reflexion in order to improve the clinical research performances, taking into account a scientific and regulatory context more and more constraining. (authors)
Watson Susan B
Full Text Available Abstract Background In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI in schizophrenia (Kane et al., 2010, apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes. Methods Outpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140, "medium" (405 mg/4 weeks; N = 318, or "high" (300 mg/2 weeks; N = 141 dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data, or the Cochran-Armitage test (categorical data. Results Safety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose, mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02], high: +3.58 [SD = 33.78] μg/L, p = .001; ES = 0.410 high vs. low dose, fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose. Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p Conclusions Analyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When
Petersen, Iver; Dietel, Manfred; Geilenkeuser, Wolf J; Mireskandari, Masoud; Weichert, Wilko; Steiger, Katja; Scheel, Andreas H; Büttner, Reinhard; Schirmacher, Peter; Warth, Arne; Lasitschka, Felix; Schildhaus, Hans-Ulrich; Kirchner, Thomas; Reu, Simone; Kreipe, Hans; Länger, Florian; Tiemann, Markus; Schulte, Christoph; Jöhrens, Korinna
EGFR and its downstream signaling pathway are important targets for cancer therapy. Recently, the monoclonal anti-EGFR antibody Necitumumab in combination with gemcitabine and cisplatin was approved (EMA/14106/2016) for first-line treatment of squamous non-small cell carcinoma (SqNSCLC). Eligibility was restricted to cases with positive EGFR expression. In this context, a ring trial of the Quality Assurance Initiative for Pathology (QuIP ® ) was launched to prepare the German pathology community for a reliable and reproducible, immunohistochemically based biomarker test. The trial was set up by a three-step approach. Two lead institutes were nominated to organize the trial process and to select appropriate cancer samples. These were first tested by the H-score (range 0-300) to identify positive and negative cases. Seven additional pathology institutes with experience in EGFR immunohistochemistry each tested the selected panel of identical cases (internal ring trial) to confirm the suitability of samples and scoring criteria. Then the open ring trial for all institutes of pathology in German speaking countries was announced. For the internal trial 8 EGFR-positive and 2 negative lung sqNSCLC samples were selected. A cut-off value of cell membranous staining in≥1% of tumor cells was introduced to define a case as EGFR negative or positive. Two points were attainable per correctly assessed sample leading to a maximum of 20 points,≥18 points were required for a successful participation. All 7 panel institute passed this barrier, 5 with the maximum of 20 points and two with one error (18 points) being related to one case with incorrect interpretation of cytoplasmic versus membranous staining and one case with an H-score of 2 as being considered EGFR positive. A second cut-off value (H-score≥3) was therefore introduced. In the open ring trial, 34 institutions participated of which 28 were successful according to the above criteria. The trial revealed a high
Schnitzbauer, A A; Lamby, P E; Mutzbauer, I; von Hassel, J; Geissler, E K; Schlitt, H J
Transplantation medicine offers multiple translational questions which should preferably be transferred to clinical evidence. The current gold standard for testing such questions and hypotheses is by prospective randomized controlled trials (RCT). The trials should be performed independently from the medical industry to avoid conflicts of interests and to guarantee a strict scientific approach. A good model is an investigator initiated trial (IIT) in which academic institutions function as the sponsor and in which normally a scientific idea stands before marketing interests of a certain medical product. We present a model for an IIT which is sponsored and coordinated by Regensburg University Hospital at 45 sites in 13 nations (SiLVER study), highlight special pitfalls of this study and offer alternatives to this approach. Finances: financial support in clinical trials can be obtained from the medical industry. Alternatively in Germany the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) offers annual grants. The expansion of financial support through foundations is desirable. Infrastructure: sponsorship within the pharmaceutics act (Arzneimittelgesetz) demands excellent infrastructural conditions and a professional team to accomplish clinical, logistic, regulatory, legal and ethical challenges in a RCT. If a large trial has sufficient financial support certain tasks can be outsourced and delegated to contract research organizations, coordinating centers for clinical trials or partners in the medical industry. Clinical scientific advances to improve evidence are an enormous challenge when performed as an IIT. However, academic sponsors can perform (international) IITs when certain rules are followed and should be defined as the gold standard when scientific findings have to be established clinically.
Haakansson, M.; Baath, M.; Boerjesson, S.; Kheddache, S.; Grahn, A.; Ruschin, M.; Tingberg, A.; Mattson, S.; Maansson, L. G.
As a part of the Europe-wide research project 'Unification of physical and clinical requirements for medical X-ray imaging' - governed by the Radiological Imaging Unification Strategies (RADIUS) Group - a major image quality trial was conducted by members of the group. The RADIUS chest trial aimed at thoroughly examining various aspects of nodule detection in digital chest radiography, such as the effects of nodule location, system noise, anatomical noise, and anatomical background. The main findings of the RADIUS chest trial concerning the detection of a lung nodule with a size in the order of 10 mm can be summarised as: (1) the detectability of the nodule is largely dependent on its location in the chest, (2) the system noise has a minor impact on the detectability at the dose levels used today, (3) the disturbance of the anatomical noise is larger than that of the system noise but smaller than that of the anatomical background and (4) the anatomical background acts as noise to a large extent and is the major image component affecting the detectability of the nodule. (authors)
Hsu, S.S.; Trávníček, Zdeněk; Chou, C.-C.; Chen, C. C.; Wang, A. B.
Roč. 203, December (2013), s. 291-299 ISSN 0924-4247 Institutional support: RVO:61388998 Keywords : synthetic jet * double-acting & single acting machines * PIV Subject RIV: BK - Fluid Dynamics Impact factor: 1.943, year: 2013 http://dx.doi.org/10.1016/j.sna.2013.09.005
This Act amends Act No. 332 of June 19, 1974 on civil liability for nuclear damage, enabling Denmark to ratify the 1982 Protocols to amend the Paris Convention and the Brussels Supplementary Convention as well as the 1988 Joint Protocol relating to the application of the Vienna and the Paris Convention. The 1988 Act raises the nuclear operator's liability from 75 million DKr to 60 million SDRs while cover involving State funds is raised from 120 million units of account to 300 million SDRs. The Act entered into force on July 1, 1989 except for the provision on State funds which becomes effective when the 1982 Protocol amending the Brussels Convention comes into force. (NEA) [fr
Full Text Available Sophisticated criminal situation with juvenile delinquency in Arkhangelsk region has prompted practitioners to find new ways to counteract. The basis for the acquisition of new knowledge in the field of prevention of juvenile delinquency was the phased introduction of social support for the pre-trial juvenile in conflict with the law. Based on the survey of investigators, investigators, judges and social workers involved in the experiment, the analysis of materials of criminal cases involving young offender’s conclusions about the positive results of the experiment revealed the difficulties and challenges faced by law enforcers. The article provides suggestions for optimizing the procedure of pre-trial support.
Laborde, Nicole D; Pleasants, Elizabeth; Reddy, Krishnaveni; Atujuna, Millicent; Nakyanzi, Teopista; Chitukuta, Miria; Naidoo, Sarita; Palanee-Phillips, Thesla; Baeten, Jared M; Montgomery, Elizabeth T
Vaginally-inserted HIV prevention methods have been reported to impact the sexual experience for women and their partners, and hence impacts acceptability of and adherence to the method. We analyzed in-depth interviews and focus group discussions about participants' sexual experiences while wearing the ring, collected during the MTN-020/ASPIRE phase 3 safety and effectiveness trial of a dapivirine vaginal ring for HIV prevention in Malawi, South Africa, Uganda, and Zimbabwe. Most women reported that partners did not feel the ring during sex, however, women felt they had to manage their partners' interaction with or reaction to the ring. In maintaining positive relationships, women were concerned about partners' discovering ring use and about ensuring that partners had a good sexual experience with them. Finally women were concerned about how they themselves experienced sex with the ring. Some found that the ring made the vaginal environment more desirable for their partners and themselves.
Pleasants, Elizabeth; Reddy, Krishnaveni; Atujuna, Millicent; Nakyanzi, Teopista; Chitukuta, Miria; Naidoo, Sarita; Palanee-Phillips, Thesla; Baeten, Jared M.; Montgomery, Elizabeth T.
Vaginally-inserted HIV prevention methods have been reported to impact the sexual experience for women and their partners, and hence impacts acceptability of and adherence to the method. We analyzed in-depth interviews and focus group discussions about participants’ sexual experiences while wearing the ring, collected during the MTN-020/ASPIRE phase 3 safety and effectiveness trial of a dapivirine vaginal ring for HIV prevention in Malawi, South Africa, Uganda, and Zimbabwe. Most women reported that partners did not feel the ring during sex, however, women felt they had to manage their partners’ interaction with or reaction to the ring. In maintaining positive relationships, women were concerned about partners’ discovering ring use and about ensuring that partners had a good sexual experience with them. Finally women were concerned about how they themselves experienced sex with the ring. Some found that the ring made the vaginal environment more desirable for their partners and themselves. PMID:29151197
Hacker, Thomas; Stone, Paul; MacBeth, Angus
Acceptance and Commitment Therapy (ACT) has accrued a substantial evidence base. Recent systematic and meta-analytic reviews suggest that ACT is effective compared to control conditions. However, these reviews appraise the efficacy of ACT across a broad range of presenting problems, rather than addressing specific common mental health difficulties. Focussing on depression and anxiety we performed a meta-analysis of trials of ACT. We incorporated sequential meta-analysis (SMA) techniques to critically appraise the sufficiency of the existing evidence base. Findings suggest that ACT demonstrates at least moderate group and pre-post effects for symptom reductions for both anxiety and depression. However using SMA findings are more qualified. There is currently insufficient evidence to confidently conclude that ACT for anxiety is efficacious when compared to active control conditions or as primary treatment for anxiety. Similarly, using SMA, there is currently insufficient evidence to suggest a moderate efficacy of ACT for depression compared to active control conditions. To stimulate further research we offer specific estimates of additional numbers of participants required to reach sufficiency to help inform future studies. We also discuss the appropriate strategies for future research into ACT for anxiety given the current evidence suggests no differential efficacy of ACT in the treatment of anxiety compared to active control conditions. Copyright © 2015 Elsevier B.V. All rights reserved.
McFee, J.N.; Dalton, J.D.; Bohrer, H.A.
The Waste Experimental Reduction Facility (WERF) was constructed to reduce the volume of low-level radioactive waste at the Idaho National Engineering Laboratory (INEL). To address the problem of radioactively contaminated ignitable hazardous waste resulting from INEL activities, a development program was carried out to evaluate WERF's ability to meet the regulated criteria for incinerating liquid and solid ignitable waste. Concurrently, INEL submitted its hazardous waste Part B application under the Resource Conservation and Recovery Act (RCRA). As required, and as a major step in the permitting process, the WERF incinerator portion of the permit application included a proposed trial burn, which is a demonstration test of the incinerator's ability to destroy hazardous materials. The trial burn plan was designed to demonstrate the system performance for liquid and solid ignitable wastes at three operating conditions, using a prepared mix of materials representative of waste to be processed. EPA Region X reviewed and commented on the plan prior to the trial burn. Results of the liquid feed trial burn showed a greater than 97% probability of meeting the RCRA-dictated DRE value for chlorinated solvents and a greater than 99% probability for nonchlorinated solvents. Nonchlorinated solid waste results were calculated at a 93% probability of meeting the required DRE, with a 75% probability for chlorinated solid wastes. In addition, the incinerator DRE continued to improve long after the assumed pre-test equilibrium period had ended. The trial burn demonstrates that the WERF incinerator can safely and adequately destroy ignitable hazardous and mixed waste and provides a significant enhancement of the INEL's waste management system
Powers, Sonya; Li, Dongmei; Suh, Hongwook; Harris, Deborah J.
ACT reporting categories and ACT Readiness Ranges are new features added to the ACT score reports starting in fall 2016. For each reporting category, the number correct score, the maximum points possible, the percent correct, and the ACT Readiness Range, along with an indicator of whether the reporting category score falls within the Readiness…
Have you ever had a biased thought? If the answer is “yes,” join the club. Everybody has biases and, although that doesn’t make us bad people, it does mean we compromise our ability to get along with people who are different from us. The good news is, there’s a lot we can do to defeat bias. Calling on Dr. Sondra Thiederman’s twenty-five years of experience in the diversity/inclusion field, the book lays out an innovative WATCH, THINK, ACT strategy that each of us can immediately apply to the task. Easy-to-read and filled with anecdotes and activities, 3 Keys shows the reader: • How to WATCH their thoughts, experiences, and actions to identify unconscious biases and target them for extinction. • How to THINK in such a way as to weaken and control our biases. • How to ACT to defeat our biases and cultivate the kind of common ground that we know to be inhospitable to the survival of bias. Designed to motivate real change, the answer to defeating our biases is in these pages. The rest is up to you...
Full Text Available Abstract Background Morning light exposure administered as simulated dawn looks a promising method to treat Seasonal Affective Disorder, but it may moreover help with resetting the inaccurate organisation of body clock functions relative to sleep occurring in winter among people in general. Disturbances in sleep patterns are common and may compromise wellbeing even in the short term. Our hypothesis was that simulated dawn could improve the subjective quality of sleep during winter. Methods A community-based trial with 100 volunteer subjects provided with dawn simulators. Study period lasted for eight weeks, and subjects used the dawn simulators for two weeks at a time, each subject acting as his own control (ABAB-design. Main outcome measure was subjective quality of sleep recorded each morning with Groningen Sleep Quality Scale. Results 77 subjects completed the trial. Quality of sleep improved while subjects were using dawn simulator-devices (p = 0.001. The treatment became beneficial after six days' use of dawn simulator, but the effect did not last after the use was ceased. Conclusion Dawn simulation may help to improve the subjective quality of sleep, but the benefits are modest. Further research is needed to verify these findings and to elucidate the mechanism by which dawn simulation acts on the sleep-wake pattern.
Timmermans, Stefan; McKay, Tara
Bioethicists have warned against the dangers of mixing research with treatment. They are concerned that research priorities may take precedence over individual patient needs and that research subjects tend to misunderstand the purpose of research or overestimate the direct medical benefits of participating in studies. Yet, other work has questioned whether clinical research can always be separated from therapeutic benefit for participants. Using in-depth interviews with participants in two phase III randomized U.S. clinical trials for methamphetamine dependency, we examine the treatment options available to participants, their experiences with participating in the trials, and potential problems of trial participation. We find that while participants have experience with four alternative treatment modalities - quitting alone, support groups, in-patient treatment facilities, and consulting primary care physicians - the randomized clinical trials compare favorably to alternatives because they provide access to evidence-based behavioral treatments, specialized medical professionals, non-judgmental staff, and the possibility of receiving an experimental drug. We conclude that while randomized clinical trials are imperfect substitutes for clinical care, they constitute a fragile and sporadic therapeutic niche in a country with fundamental problems in access to health care, a mixed punitive-therapeutic drug addiction policy, and a profit-driven pharmaceutical development and approval process.
Full Text Available The continued participation of volunteers in clinical trials is crucial to advances in healthcare. Few data are available regarding the satisfaction and impressions of healthy volunteers after participation in phase I trials, many of which lead to unexpected adverse events. We report feedback from over 100 adult volunteers who took part in a first-in-human trial conducted in a high-income country testing an experimental Ebola vaccine causing significant reactogenicity, as well as unexpected arthritis in one fifth of participants. The anonymous, internet-based satisfaction survey was sent by email to all participants upon their completion of this one-year trial; it asked 24 questions concerning volunteers' motivations, impressions of the trial experience, and overall satisfaction. Answers were summarized using descriptive statistics. Of the 115 trial participants, 103 (90% filled out the survey. Fifty-five respondents (53% were male. Thirty-five respondents (34% were healthcare workers, many of whom would deploy to Ebola-affected countries. All respondents cited scientific advancement as their chief motivation for participation, while 100/103 (97% and 61/103 (59% reported additional "humanitarian reasons" and potential protection from Ebolavirus, respectively. Although investigators had documented adverse events in 97% of trial participants, only 74 of 103 respondents (72% recalled experiencing an adverse event. All reported an overall positive experience, and 93/103 (90% a willingness to participate in future trials. Given the high level of satisfaction, no significant associations could be detected between trial experiences and satisfaction, even among respondents reporting adverse events lasting weeks or months. Despite considerable reactogenicity and unexpected vaccine-related arthritis, all survey respondents reported overall satisfaction. While this trial's context was unique, the positive feedback is likely due at least in part to the
Cherry, Todd L.; Kallbekken, Steffen; Kroll, Stephen
This paper examines the political difficulty of enacting welfare-enhancing Pigouvian taxes. Using referenda in a market experiment with externalities, we investigate the effect of trial periods on the acceptability of two theoretically equivalent variants of Pigouvian taxes. While implementing either tax is in subjects material self-interest, we find significant levels of opposition to both tax schemes, though the level differs considerably. Results show that trial runs can overcome initial tax aversion, significantly increasing acceptability. The effect is robust across tax schemes, but a trial with one scheme does not affect the acceptability of the other. Trial periods also mitigate initial biases in preferences of alternative tax schemes. (auth)
Franzè, S; Cilurzo, F; Minghetti, P
The impending expiration of patent protection for recombinant insulins provides the opportunity to introduce cost-saving copies, named biosimilars, onto the market. Although there is broad experience in the production and characterisation of insulins, the development of copies is still a challenge. In this paper, the main features of insulins and the EU regulatory framework for their biosimilar products are reviewed. The main focus is on rapid-acting insulin analogues (Humalog(®); Novolog(®)/NovoRapid(®); Apidra(®)). Since they differ by one or two amino acids in chain B, production of one biosimilar for all three drug products is not feasible. However, from post-marketing-collected clinical data, rapid-acting insulin analogues seem to have similar therapeutic efficacy. It is reasonable to suppose that, for prescription to treatment-naïve patients, the cheaper biosimilar would be the preferred choice of physicians, either spontaneously or induced by health insurance. Therefore, its introduction will affect the market share of all the other rapid-acting insulin analogues.
Whitesides, Louisa W; Baren, Jill M; Biros, Michelle H; Fleischman, Ross J; Govindarajan, Prasanthi R; Jones, Elizabeth B; Pancioli, Arthur M; Pentz, Rebecca D; Scicluna, Victoria M; Wright, David W; Dickert, Neal W
Evidence suggests that patients are generally accepting of their enrollment in trials for emergency care conducted under exception from informed consent. It is unknown whether individuals with more severe initial injuries or worse clinical outcomes have different perspectives. Determining whether these differences exist may help to structure post-enrollment interactions. Primary clinical data from the Progesterone for the Treatment of Traumatic Brain Injury trial were matched to interview data from the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study. Answers to three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study were analyzed in the context of enrolled patients' initial injury severity (initial Glasgow Coma Scale and Injury Severity Score) and principal clinical outcomes (Extended Glasgow Outcome Scale and Extended Glasgow Outcome Scale relative to initial injury severity). The three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study addressed participants' general attitude toward inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial (general trial inclusion), their specific attitude toward being included in Progesterone for the Treatment of Traumatic Brain Injury trial under the exception from informed consent (personal exception from informed consent enrollment), and their attitude toward the use of exception from informed consent in the Progesterone for the Treatment of Traumatic Brain Injury trial in general (general exception from informed consent enrollment). Qualitative analysis of interview transcripts was performed to provide contextualization and to determine the extent to which respondents framed their attitudes in terms of clinical experience. Clinical data from Progesterone for the Treatment of Traumatic Brain Injury
James, J S
A clinical trial using remune, the anti-HIV vaccine developed by the late Dr. Jonas Salk, has been ended. The study is a clinical-endpoint trial which looks for statistically significant differences in AIDS sickness or death between patients who add remune to their treatment regimens versus those who use a placebo. Agouron Pharmaceuticals and the Immune Response Corporation who were conducting the trial announced their decision to stop it after an analysis by the Data Safety Monitoring Board. No differences in clinical endpoints were found and it was projected that continuing the trial would likely not find any. The companies are now planning two new Phase III trials using viral load testing rather than clinical endpoints as study criteria.
Thomas, Kim S; Koller, Karin; Foster, Katharine; Perdue, Jo; Charlesworth, Lisa; Chalmers, Joanne R
Following the successful introduction of five topic-specific research networks in the UK, the Comprehensive Local Research Network (CLRN) was established in 2008 in order to provide a blanket level of support across the whole country regardless of the clinical discipline. The role of the CLRN was to facilitate recruitment into clinical trials, and to encourage greater engagement in research throughout the National Health Service (NHS). This report evaluates the impact of clinical research networks in supporting clinical trials in the UK, with particular reference to our experiences from two non-commercial dermatology trials. It covers our experience of engaging with the CLRN (and other research networks) using two non-commercial dermatology trials as case studies. We present the circumstances that led to our approach to the research networks for support, and the impact that this support had on the delivery of these trials. In both cases, recruitment was boosted considerably following the provision of additional support, although other factors such as the availability of experienced personnel, and the role of advertising and media coverage in promoting the trials were also important in translating this additional resource into increased recruitment. Recruitment into clinical trials is a complex task that can be influenced by many factors. A world-class clinical research infrastructure is now in place in England (with similar support available in Scotland and Wales), and it is the responsibility of the research community to ensure that this unique resource is used effectively and responsibly.
Full Text Available ... of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key ... Enterprise NHLBI has a strong tradition of supporting clinical trials that have not only shaped medical practice around the world, but have improved the health ...
Kryscio, R J; Abner, E L; Schmitt, F A; Goodman, P J; Mendiondo, M; Caban-Holt, A; Dennis, B C; Mathews, M; Klein, E A; Crowley, J J
.0%) of the sites chose to participate in PREADViSE. Staff turnover at the sites presented challenges when training persons unfamiliar with cognitive testing procedures to conduct the memory screens. In the RCT few participants (1.6%) failed the MIS screen and among those who passed this screen a significant practice effect was encountered. In the exposure study 3,581 men were reached by phone in year 1, 15.7% could not be reached after 5 calls, and of those contacted 6.0% refused the screen even after consenting to the procedures at their clinical site. Most notable is that the failure rate for the MIS-T increased fourfold to 7.2%. Of the 257 men who took the TICS-M, 84.0% failed and were asked to contact their physicians for a more detailed memory assessment, and approximately half of these had some form of dementia or cognitive impairment. Several of these dementia cases are not AD. Partnering with SELECT led to an AD prevention trial conducted at a very reasonable cost by taking advantage of the experience and efficient clinical trial management found in a cancer cooperative group (Southwest Oncology Group or SWOG). Once unblinded, the RCT and exposure study data have the potential to yield new information on long term exposure to antioxidant supplements under controlled conditions.
Mehta, M.P.; Adak, S.; Wagner, H.; Cella, D.
PURPOSE: To gain experience in measuring quality of life (QOL) using the FACT-L in patients (pt) with non small cell lung cancer (NSCLC) treated with an altered fractionation regimen, HART, in a Phase II, multiinstitutional ECOG trial. MATERIALS AND METHODS: Version 2 of FACT-L, with 43 questions in 6 subscale categories (8 physical well-being, 8 social/family well-being, 3 relationship with doctor, 6 emotional well-being, 8 functional well-being, 10 lung cancer symptoms), available in English, Spanish and French, was administered by data managers and filled out by pts, independent of physician presence or input. The HART trial enrolled 30 pts, and FACT-L was administered at baseline (tp 1), treatment completion (tp 2) and 4 weeks following therapy (tp 3). (35(43)) FACT-L items were designed to yield a total QOL score with higher values reflective of better QOL; in addition, a FACT-L trial outcome index (TOI) was computed (TOI = physical score + functional score + lung cancer related score), and is considered the most relevant clinical QOL measure. RESULTS: The FACT-L completion rates were: tp 1 - (30(30)) (100%), tp 2 - (29(30)) (97%) and tp 3 - (24(30)) (80%); the mean scores at various time points are summarized in the table below and indicate that FACT-L is responsive to changes over time. The differences in subscales and total scores can be used as a measure of change in QOL resulting from treatment; statistically significant change was noted from baseline to tp 2 for physical, emotional and functional well-being; and from baseline to tp 3 for emotional well-being. The change in TOI score was also evaluated as a function of response and toxicity grade, and no clear association emerged. When assessed as a function of survival (at the time of this analysis, (5(30)) pt were alive, with median survival of 56 weeks), the degradation in QOL was most severe for pt who died early; the mean change in TOI from baseline to tp 3 for pt dying in the first 25 weeks, 25
Beattie, Jill; Hall, Helen; Biro, Mary Anne; East, Christine; Lau, Rosalind
To determine the feasibility and acceptability and measure the effects of a mindfulness intervention compared to a pregnancy support program on stress, depressive symptoms and awareness of present moment experience. A pilot randomised trial using mixed methods. Forty-eight women attending a maternity service were randomly allocated to a mindfulness-based or pregnancy support program. Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Mindfulness Attention Awareness Scale, and Birth Outcomes. Women's perceptions of the impact of the programs were examined via summative evaluation, interviews, diaries and facilitator field notes. Nine women in the mindfulness program and 11 in the pregnancy support program completed post-program measures. There were no statistically significant differences between groups. Of practical significance, was an improvement in measures for both groups with a greater improvement in awareness of present moment experience for the intervention group. The intervention group reported learning how to manage stressors, fear, anxiety, and to regulate their attention to be more present. The control group reported learning how to calm down when stressed which increased their confidence. Intervention group themes were: releasing stress, becoming aware, accepting, having options and choices, connecting and being compassionate. Control group themes were:managing stress, increasing confidence, connecting, focussing, being accepted, preparing. The feasibility and acceptability of the intervention was confirmed. Programs decreased women's self-reported stress in different ways. Women in the mindfulness program accepted themselves and their experiences as they arose and passed in the present moment, while those in the control group gained acceptance primarily from external sources such as peers. Mindfulness programs can foster an internalised locus of self-acceptance which may result in woman becoming less dependent on others for their wellbeing
Eilifsen, Christoffer; Arntzen, Erik
Some studies which have shown that differences in outcome on tests for stimulus equivalence dependent on different training structures, have run the tests as separate blocks without baseline trials interspersed in between test trials. Saunders and co-workers have argued that the differences in test outcome could be related to differences in the retention of trained discriminations during testing (R. R. Saunders, Drake, & Spradlin, 1999; R. R. Saunders & Green, 1999). In the current experiment...
Full Text Available This paper focuses on how migrant youth in Melbourne with experience of direct or indirect migration negotiate cross-cultural engagements and tensions between family, community and the greater society in which they are supposed to participate as political subjects. It examines whether the meaning and interpretation of citizenship in Australia allows migrant youth to act as full and active citizens with all the contradictions and difficulties inherent in acting as “a bridge between two worlds”. By voicing the personalised journeys of young people dealing with uneasy questions of displacement, identity and belonging, this paper examines the complex ways through which migrant youth negotiate and in some cases bridge intercultural tensions within a multicultural society.
Giovanni Pagano; Annarita Aiello Talamanca; Giuseppe Castello; Mario D. Cordero; Marco d'Ischia; Maria Nicola Gadaleta; Federico V. Pallardó; Sandra Petrović; Luca Tiano; Adriana Zatterale
An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluat...
... Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices... AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.1 Act. Act and Export Apple Act are synonymous and mean “An act to promote the foreign trade of the United States in apples to protect the reputation of...
Gheza, Federico; Raimondi, Paolo; Solaini, Leonardo; Coccolini, Federico; Baiocchi, Gian Luca; Portolani, Nazario; Tiberio, Guido Alberto Massimo
Outside the US, FLS certification is not required and its teaching methods are not well standardized. Even if the FLS was designed as "stand alone" training system, most of Academic Institution offer support to residents during training. We present the first systematic application of FLS in Italy. Our aim was to evaluate the role of mentoring/coaching on FLS training in terms of the passing rate and global performance in the search for resource optimization. Sixty residents in general surgery, obstetrics & gynecology, and urology were selected to be enrolled in a randomized controlled trial, practicing FLS with the goal of passing a simulated final exam. The control group practiced exclusively with video material from SAGES, whereas the interventional group was supported by a mentor. Forty-six subjects met the requirements and completed the trial. For the other 14 subjects no results are available for comparison. One subject for each group failed the exam, resulting in a passing rate of 95.7%, with no obvious differences between groups. Subgroup analysis did not reveal any difference between the groups for FLS tasks. We confirm that methods other than video instruction and deliberate FLS practice are not essential to pass the final exam. Based on these results, we suggest the introduction of the FLS system even where a trained tutor is not available. This trial is the first single institution application of the FLS in Italy and one of the few experiences outside the US. Trial Number: NCT02486575 ( https://www.clinicaltrials.gov ).
Background Qualitative research is undertaken with randomized controlled trials of health interventions. Our aim was to explore the perceptions of researchers with experience of this endeavour to understand the added value of qualitative research to the trial in practice. Methods A telephone semi-structured interview study with 18 researchers with experience of undertaking the trial and/or the qualitative research. Results Interviewees described the added value of qualitative research for the trial, explaining how it solved problems at the pretrial stage, explained findings, and helped to increase the utility of the evidence generated by the trial. From the interviews, we identified three models of relationship of the qualitative research to the trial. In ‘the peripheral’ model, the trial was an opportunity to undertake qualitative research, with no intention that it would add value to the trial. In ‘the add-on’ model, the qualitative researcher understood the potential value of the qualitative research but it was viewed as a separate and complementary endeavour by the trial lead investigator and wider team. Interviewees described how this could limit the value of the qualitative research to the trial. Finally ‘the integral’ model played out in two ways. In ‘integral-in-theory’ studies, the lead investigator viewed the qualitative research as essential to the trial. However, in practice the qualitative research was under-resourced relative to the trial, potentially limiting its ability to add value to the trial. In ‘integral-in-practice’ studies, interviewees described how the qualitative research was planned from the beginning of the study, senior qualitative expertise was on the team from beginning to end, and staff and time were dedicated to the qualitative research. In these studies interviewees described the qualitative research adding value to the trial although this value was not necessarily visible beyond the original research team due
O'Cathain, Alicia; Goode, Jackie; Drabble, Sarah J; Thomas, Kate J; Rudolph, Anne; Hewison, Jenny
Qualitative research is undertaken with randomized controlled trials of health interventions. Our aim was to explore the perceptions of researchers with experience of this endeavour to understand the added value of qualitative research to the trial in practice. A telephone semi-structured interview study with 18 researchers with experience of undertaking the trial and/or the qualitative research. Interviewees described the added value of qualitative research for the trial, explaining how it solved problems at the pretrial stage, explained findings, and helped to increase the utility of the evidence generated by the trial. From the interviews, we identified three models of relationship of the qualitative research to the trial. In 'the peripheral' model, the trial was an opportunity to undertake qualitative research, with no intention that it would add value to the trial. In 'the add-on' model, the qualitative researcher understood the potential value of the qualitative research but it was viewed as a separate and complementary endeavour by the trial lead investigator and wider team. Interviewees described how this could limit the value of the qualitative research to the trial. Finally 'the integral' model played out in two ways. In 'integral-in-theory' studies, the lead investigator viewed the qualitative research as essential to the trial. However, in practice the qualitative research was under-resourced relative to the trial, potentially limiting its ability to add value to the trial. In 'integral-in-practice' studies, interviewees described how the qualitative research was planned from the beginning of the study, senior qualitative expertise was on the team from beginning to end, and staff and time were dedicated to the qualitative research. In these studies interviewees described the qualitative research adding value to the trial although this value was not necessarily visible beyond the original research team due to the challenges of publishing this research
Huff, Robin A; Maca, Jeff D; Puri, Mala; Seltzer, Earl W
BackgroundPediatric clinical trials commonly experience recruitment challenges including limited number of patients and investigators, inclusion/exclusion criteria that further reduce the patient pool, and a competitive research landscape created by pediatric regulatory commitments. To overcome these challenges, innovative approaches are needed.MethodsThis article explores the use of Bayesian statistics to improve pediatric trial feasibility, using pediatric Type-2 diabetes as an example. Data for six therapies approved for adults were used to perform simulations to determine the impact on pediatric trial size.ResultsWhen the number of adult patients contributing to the simulation was assumed to be the same as the number of patients to be enrolled in the pediatric trial, the pediatric trial size was reduced by 75-78% when compared with a frequentist statistical approach, but was associated with a 34-45% false-positive rate. In subsequent simulations, greater control was exerted over the false-positive rate by decreasing the contribution of the adult data. A 30-33% reduction in trial size was achieved when false-positives were held to less than 10%.ConclusionReducing the trial size through the use of Bayesian statistics would facilitate completion of pediatric trials, enabling drugs to be labeled appropriately for children.
Majhail, Navneet S; Giralt, Sergio; Bonagura, Anthony; Crawford, Stephen; Farnia, Stephanie; Omel, James L; Pasquini, Marcelo; Saber, Wael; LeMaistre, Charles F
The Patient Protection and Affordable Care Act requires that health care insurers cover routine patient costs associated with participating in clinical trials for cancer and other life-threatening diseases. There is a need to better define routine costs within the context of hematopoietic stem cell transplantation (HSCT) clinical trials. This white paper presents guidance on behalf of the American Society for Blood and Marrow Transplantation for defining a standard HSCT episode and delineates components that may be considered as routine patient costs versus research costs. The guidelines will assist investigators, trial sponsors, and transplantation centers in planning for clinical trials that are conducted as a part of the HSCT episode and will inform payers who provide coverage for transplantation. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Daddy, Nsengiyumva Bati; Kalisya, Luc Malemo; Bagire, Pascal Gisenya; Watt, Robert L; Towler, Melissa J; Weathers, Pamela J
Dried leaf Artemisia annua (DLA) has shown efficacy against Plasmodium sp. in rodent studies and in small clinical trials. Rodent malaria also showed resiliency against the evolution of artemisinin drug resistance. This is a case report of a last resort treatment of patients with severe malaria who were responding neither to artemisinin combination therapy (ACT) nor i.v. artesunate. Of many patients treated with ACTs and i.v. artesunate during the 6 mon study period, 18 did not respond and were subsequently treated with DLA Artemisia annua. Patients were given a dose of 0.5g DLA per os, twice daily for 5d. Total adult delivered dose of artemisinin was 55mg. Dose was reduced for body weight under 30kg. Clinical symptoms, e.g. fever, coma etc., and parasite levels in thick blood smears were tracked. Patients were declared cured and released from hospital when parasites were microscopically undetectable and clinical symptoms fully subsided. All patients were previously treated with Coartem® provided through Santé Rurale (SANRU) and following the regimen prescribed by WHO. Of 18 ACT-resistant severe malaria cases compassionately treated with DLA, all fully recovered. Of the 18, this report details two pediatric cases. Successful treatment of all 18 ACT-resistant cases suggests that DLA should be rapidly incorporated into the antimalarial regimen for Africa and possibly wherever else ACT resistance has emerged. Copyright © 2017. Published by Elsevier GmbH.
Stephan S Terblanche
Full Text Available In this contribution a number of procedural issues related to the sentencing of child offenders and emanating from the Child Justice Act 75 of 2008 are considered in some detail. As a general rule, the Act requires pre-sentence reports to be obtained from probation officers before sentencing any child offender, with only a limited number of exceptions. The article argues that the peremptory nature of the Act means that a probation report is always required, even if reports by other experts are also available. The exceptions are limited to instances other than those where the child offender is sentenced to any form of imprisonment or to residence in a care centre. The article addresses the question of whether or not the reference to imprisonment includes alternative imprisonment which is imposed only as an alternative to a fine. It suggests that alternative imprisonment should, generally, not be imposed on child offenders. When an exception is not prevented because of the sentence, a pre-sentence report may be dispensed with only when the offence is a schedule-1 offence (the least serious class of offences or when obtaining a report would prejudice the child. It is argued that these exceptions are likely to occur rather rarely. A final aspect of the Act’s provisions on pre-sentence reports is the requirement that reasons be given for a departure from the recommendations in a pre-sentence report. This requirement merely confirms the status quo.The Act permits the prosecutor to provide the court with a victim impact statement. Such a statement is defined in the Act. It is a sworn statement by a victim or someone authorised by the victim explaining the consequences to the victim of the commission of the crime. The article also addresses the issue of whether or not the child justice court might mero motu obtain a victim impact statement when the prosecution does not do so.Finally, the article addresses appeals against and reviews of the trial
Full Text Available ... clinical trials. If you're thinking about taking part in a clinical trial, find out ahead of time about costs and coverage. You should learn about the risks and benefits of any clinical trial before you agree to take part in the trial. Talk with your doctor about ...
Khurshid, Ayesha; Jacquin, Kristine M
We examined the impact of expert witness orientation (researcher or clinical practitioner) and type of testimony (testimony for the prosecution, defense, both prosecution and defense, or no testimony) on mock jurors' decisions in a sexual abuse trial. Participants acted as mock jurors on a sexual abuse criminal trial based on recovered memory that included expert witness testimony. Results showed that expert witness testimony provided by a researcher did not impact mock jurors' guilt ratings any differently than the expert witness testimony provided by a clinical practitioner. However, type of testimony had a significant effect on jurors' guilt ratings such that jurors who read only defense or only prosecution testimony made decisions favoring the relevant side.
The Food Safety Modernization Act improves oversight of America's food safety system. Title III, which regulates imported food, may create extra burdens for importers and therefore act as a barrier to trade. What will be on trial before the World Trade Organization (WTO), however, is not the law's content, but the science supporting it. Under the WTO regime, food safety laws that could restrict the free movement of food commodities must be sufficiently justified by scientific evidence. Member states must engage in risk assessments and regulate food imports in a manner that is "no more restrictive than necessary" to protect against the health risks identified by scientific evidence. This article examines the requirements of the WTO to evaluate the FSMA's legality under WTO rules. It analyzes the case law of the WTO Panel and Appellate Body and compares the FMSA to the EU's General Food Law.
... 7 Agriculture 2 2010-01-01 2010-01-01 false Act. 35.1 Section 35.1 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices... Definitions § 35.1 Act. Act or Export Grape and Plum Act means “An Act to promote the foreign trade of the...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 987.2 Section 987.2 Agriculture Regulations of... RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Definitions § 987.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of...
Allareddy, Veerasathpurush; Rampa, Sankeerth; Masoud, Mohamed I; Lee, Min Kyeong; Nalliah, Romesh; Allareddy, Veerajalandhar
The Food and Drug Administration Modernization Act of 1997 made it mandatory for all phase II through IV trials regulated by this Act to be registered. After this, the National Institutes of Health created ClinicalTrials.gov, which is a registry of publicly and privately supported clinical studies of human participants. The objective of this study was to examine the characteristics of registered studies in orthodontics. The ClinicalTrials.gov Web site was used to query all registered orthodontic studies. The search term used was "orthodontics." No limitations were placed for the time period. All registered studies regardless of their recruitment status, study results, and study type were selected for analysis. A total of 64 orthodontic studies were registered as of January 1, 2014. Of these, 52 were interventional, and 12 were observational. Close to 60% of the interventional studies and 66.7% of the observational studies had sample sizes of 50 or fewer subjects. About 21.2% of the interventional studies and 16.7% of the observational studies had sample sizes greater than 100. Only 1 study was funded by the National Institutes of Health, and the rest were funded by "other" or "industry" sources. Close to 87.7% of the interventional studies were randomized. Interventional model assignments included factorial assignment (3.9%), parallel assignments (74.5%), crossover assignment (7.8%), and single-group assignment (13.7%). Most studies were treatment oriented (80.4%). The types of masking used by the interventional studies included open label (28.9%), single blind (44.2%), and double blind (26.9%). Outcome assessors were blinded in only 6 studies. Orthodontic studies registered in ClinicalTrials.gov are dominated by small single-center studies. There are wide variations with regard to treatment allocation approaches and randomization methods in the studies. These results also indicate the need for multicenter clinical studies in orthodontics. Copyright © 2014
Julian M Somers
Full Text Available No previous experimental trials have investigated Housing First (HF in both scattered site (SHF and congregate (CHF formats. We hypothesized that CHF and SHF would be associated with a greater percentage of time stably housed as well as superior health and psychosocial outcomes over 24 months compared to treatment as usual (TAU.Inclusion criteria were homelessness, mental illness, and high need for support. Participants were randomised to SHF, CHF, or TAU. SHF consisted of market rental apartments with support provided by Assertive Community Treatment (ACT. CHF consisted of a single building with supports equivalent to ACT. TAU included existing services and supports.Of 800 people screened, 297 were randomly assigned to CHF (107, SHF (90, or TAU (100. The percentage of time in stable housing over 24 months was 26.3% in TAU (reference; 95% confidence interval (CI = 20.5, 32.0, compared to 74.3% in CHF (95% CI = 69.3, 79.3, p<0.001 and 74.5% in SHF (95% CI = 69.2, 79.7, p<0.001. Secondary outcomes favoured CHF but not SHF compared to TAU.HF in scattered and congregate formats is capable of achieving housing stability among people experiencing major mental illness and chronic homelessness. Only CHF was associated with improvement on select secondary outcomes.Current Controlled Trials: ISRCTN57595077.
Zannad, Faiez; Pfeffer, Marc A; Bhatt, Deepak L; Bonds, Denise E; Borer, Jeffrey S; Calvo-Rojas, Gonzalo; Fiore, Louis; Lund, Lars H; Madigan, David; Maggioni, Aldo Pietro; Meyers, Catherine M; Rosenberg, Yves; Simon, Tabassome; Stough, Wendy Gattis; Zalewski, Andrew; Zariffa, Nevine; Temple, Robert
Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Wang, Daniel Wei L; Ferraz, Octavio Luiz Motta
This paper discusses the post-trial access to drugs for patients who participated in clinical trials in Brazil. The ethical guidance for clinical trials in Brazil is arguably one of the clearest in the world in attributing to research sponsors the responsibility for providing post-trial drugs to patients who participated in their experiments. The Federal Constitution recognizes health as a fundamental right to be fulfilled by the State. Based on the Brazilian constitution and on the National Health Council resolutions, courts have been accepting patients' claims and ordering the State and the pharmaceutical companies to provide these patients with the tested treatment in the quantity and duration they need it. This generous interpretation of the duties of the pharmaceutical companies and the State makes the Brazilian model for post-trial access unique when compared to the experience of other countries and thus should be followed with attention by future research in order to assess its consequences for patients, research sponsors, and the public health system. © 2012 American Society of Law, Medicine & Ethics, Inc.
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 917.2 Section 917.2 Agriculture Regulations of... Order Regulating Handling Definitions § 917.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended, and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as...
... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1260.128 Section 1260.128 Agriculture... Promotion and Research Order Definitions § 1260.128 Act. Act means the Beef Promotion and Research Act of 1985, Title XVI, Subtitle A of the Food Security Act of 1985, Pub. L. 99-198 and any amendments thereto. ...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 906.2 Section 906.2 Agriculture Regulations of... GRANDE VALLEY IN TEXAS Order Regulating Handling Definitions § 906.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as re-enacted and amended by the Agricultural Marketing Agreement Act of...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 946.2 Section 946.2 Agriculture Regulations of... Regulating Handling Definitions § 946.2 Act. Act means Public Act No. 10, 73d Congress, as amended and reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 989.2 Section 989.2 Agriculture Regulations of... CALIFORNIA Order Regulating Handling Definitions § 989.2 Act. Act means Public Act No. 10, 73d Congress, as amended, and as re-enacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 922.2 Section 922.2 Agriculture Regulations of... WASHINGTON Order Regulating Handling Definitions § 922.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of...
Chan, C. M. C.; Scheinman, J. I.; Roth, K. S.
As the powerful tools of molecular biology continue to delineate new concepts of pathogenesis of diseases, new molecular-level therapeutic modalities are certain to emerge. In order to design and execute clinical trials to evaluate outcomes of these new treatment modalities, we will soon need a new supply of investigators with training and experience in clinical research. The slowly-progressive nature of chronic pediatric kidney disease often results in diagnosis being made at a time remote from initial result, and the inherently slow rate of progression makes changes difficult to measure. Thus, development of molecular markers for both diagnosis and rate of progression will be critical to studies of new therapeutic modalities. We will review general aspects of clinical trials and will use current and past studies as examples to illustrate specific points, especially as these apply to chronic kidney disease associated with obstructive uropathy in children. (author)
Murray, Elizabeth; McAdam, Rodney
This article compares and contrasts the main quality standards in the highly regulated pharmaceutical industry with specific focus on Good Clinical Practice (GCP), the standard for designing, conducting, recording and reporting clinical trials involving human participants. Comparison is made to ISO quality standards, which can be applied to all industries and types of organisation. The study is then narrowed to that of contract research organisations (CROs) involved in the conduct of clinical trials. The paper concludes that the ISO 9000 series of quality standards can act as a company-wide framework for quality management within such organisations by helping to direct quality efforts on a long-term basis without any loss of compliance. This study is valuable because comparative analysis in this domain is uncommon.
Full Text Available ... need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in ... Maryland, runs clinical trials. Many other clinical trials take place in medical centers and ... trial can have many benefits. For example, you may gain access to new treatments before ...
Victoria Jane Palmer
Full Text Available Background: Process evaluations are essential to understand the contextual, relational, and organizational and system factors of complex interventions. The guidance for developing process evaluations for randomized controlled trials (RCTs has until recently however, been fairly limited. Method/Design: A nested process evaluation (NPE was designed and embedded across all stages of a stepped wedge cluster RCT called the CORE study. The aim of the CORE study is to test the effectiveness of an experience-based codesign methodology for improving psychosocial recovery outcomes for people living with severe mental illness (service users. Process evaluation data collection combines qualitative and quantitative methods with four aims: (1 to describe organizational characteristics, service models, policy contexts, and government reforms and examine the interaction of these with the intervention; (2 to understand how the codesign intervention works, the cluster variability in implementation, and if the intervention is or is not sustained in different settings; (3 to assist in the interpretation of the primary and secondary outcomes and determine if the causal assumptions underpinning the codesign interventions are accurate; and (4 to determine the impact of a purposefully designed engagement model on the broader study retention and knowledge transfer in the trial. Discussion: Process evaluations require prespecified study protocols but finding a balance between their iterative nature and the structure offered by protocol development is an important step forward. Taking this step will advance the role of qualitative research within trials research and enable more focused data collection to occur at strategic points within studies.
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 956.2 Section 956.2 Agriculture Regulations of... OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Definitions § 956.2 Act. Act means Public Act No. 10... Agreement Act of 1937, as amended (Sec. 1-19, 48 Stat. 31, as amended; 7 U.S.C. 601 et seq.). ...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 983.2 Section 983.2 Agriculture Regulations of... NEW MEXICO Definitions § 983.2 Act. Act means Public Act No. 10, 73rd Congress (May 12, 1933), as amended and as re-enacted and amended by the Agricultural Marketing Order Act of 1937, as amended (48 Stat...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 930.1 Section 930.1 Agriculture Regulations of... Definitions § 930.1 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended, and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 984.2 Section 984.2 Agriculture Regulations of... Handling Definitions § 984.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (7 U.S.C. 601 et seq.). ...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 925.2 Section 925.2 Agriculture Regulations of... SOUTHEASTERN CALIFORNIA Definitions § 925.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 915.2 Section 915.2 Agriculture Regulations of... Regulating Handling Definitions § 915.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 959.2 Section 959.2 Agriculture Regulations of... Handling Definitions § 959.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (sections 1-19, 48 Stat...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 905.2 Section 905.2 Agriculture Regulations of... TANGELOS GROWN IN FLORIDA Order Regulating Handling Definitions § 905.2 Act. Act means Public Act No. 10... Agreement Act of 1937, as amended. (48 Stat. 31, as amended; 7 U.S.C. 601 et seq.; 68 Stat. 906, 1047.) ...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 955.2 Section 955.2 Agriculture Regulations of... § 955.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (Sec. 1-19, 48 Stat. 31, as...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 982.2 Section 982.2 Agriculture Regulations of... Order Regulating Handling Definitions § 982.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (7 U.S.C...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 932.2 Section 932.2 Agriculture Regulations of... Handling Definitions § 932.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933) as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 981.2 Section 981.2 Agriculture Regulations of... Handling Definitions § 981.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as amended...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 966.2 Section 966.2 Agriculture Regulations of... Handling Definitions § 966.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48 Stat. 31, as amended...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 916.2 Section 916.2 Agriculture Regulations of... Regulating Handling Definitions § 916.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 993.2 Section 993.2 Agriculture Regulations of... Regulating Handling Definitions § 993.2 Act. Act means Public Act No. 10, 73d Congress, as amended and reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (7 U.S.C. 601 et seq.). ...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 929.2 Section 929.2 Agriculture Regulations of... ISLAND IN THE STATE OF NEW YORK Order Regulating Handling Definitions § 929.2 Act. Act means Public Act... Marketing Agreement Act of 1937, as amended (secs. 1-19, 48 Stat. 31, as amended; 7 U.S.C. 601-674). ...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 923.2 Section 923.2 Agriculture Regulations of... IN WASHINGTON Order Regulating Handling Definitions § 923.2 Act. Act means Public Act No. 10, 73d... Act of 1937, as amended (48 Stat. 31, as amended; 7 U.S.C. 601 et seq.; 68 Stat. 906, 1047). ...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 927.2 Section 927.2 Agriculture Regulations of... Regulating Handling Definitions § 927.2 Act. Act means Public Act No. 10, 73d Congress (May 12, 1933), as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (48...
... 7 Agriculture 9 2010-01-01 2009-01-01 true Act. 1170.2 Section 1170.2 Agriculture Regulations of... Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PRODUCT MANDATORY REPORTING § 1170.2 Act. Act means the Agricultural Marketing Act of 1946, 7 U.S.C. 1621 et seq., as amended by the Dairy Market Enhancement Act of...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 953.2 Section 953.2 Agriculture Regulations of... Order Regulating Handling Definitions § 953.2 Act. Act means Public Act No. 10, 73d Congress, as amended and as re-enacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (7 U.S.C...
... 7 Agriculture 9 2010-01-01 2009-01-01 true Act. 1160.101 Section 1160.101 Agriculture Regulations... Definitions § 1160.101 Act. Act means the Fluid Milk Promotion Act of 1990, Subtitle H of Title XIX of the Food, Agriculture, Conservation, and Trade Act of 1990, Public Law 101-624, 7 U.S.C. 6401-6417, and any...
... 7 Agriculture 8 2010-01-01 2010-01-01 false Act. 948.2 Section 948.2 Agriculture Regulations of... Regulating Handling Definitions § 948.2 Act. Act means Public Act No. 10 73d Congress, as amended and as reenacted and amended by the Agricultural Marketing Agreement Act of 1937, as amended (sections 1-19, 48...
Rodrigues, H C M L; Deprest, J; v d Berg, P P
In this article, we reflect on whether randomized controlled trials (RCTs) are adequate for the clinical evaluation of maternal-fetal surgery for congenital diaphragmatic hernia (CDH), focusing on the role of patients' preferences in the setting up of research protocols, on the requirement of equipoise and on the concept of therapeutic misconception (TM). We describe the conception and setting up of the tracheal occlusion (TO) to accelerate lung growth trial and analyze the ethical dilemmas fac