168 research outputs found
Longitudinal study of informed consent in innovative therapy research: experience and provisional recommendations from a multicenter trial of intracerebral grafting.
BACKGROUND: There is an urgent need to assess and improve the consent process in clinical trials of innovative therapies for neurodegenerative disorders.
METHODS: We performed a longitudinal study of the consent of Huntington's disease patients during the Multicenter Fetal Cell Intracerebral Grafting Trial in Huntington's Disease (MIG-HD) in France and Belgium. Patients and their proxies completed a consent questionnaire at inclusion, before signing the consent form and after one year of follow-up, before randomization and transplantation. The questionnaire explored understanding of the protocol, satisfaction with the information delivered, reasons for participating in the trial and expectations regarding the transplant. Forty-six Huntington's disease patients and 27 proxies completed the questionnaire at inclusion, and 27 Huntington's disease patients and 16 proxies one year later.
RESULTS: The comprehension score was high and similar for Huntington's disease patients and proxies at inclusion (72.6% vs 77.8%; P > 0.1) but only decreased in HD patients after one year. The information satisfaction score was high (73.5% vs 66.5%; P > 0.1) and correlated with understanding in both patients and proxies. The motivation and expectation profiles were similar in patients and proxies and remained unchanged after one year.
CONCLUSIONS: Cognitively impaired patients with Huntington's disease were capable of consenting to participation in this trial. This consent procedure has presumably strengthened their understanding and should be proposed before signing the consent form in future gene or cell therapy trials for neurodegenerative disorders. Because of the potential cognitive decline, proxies should be designated as provisional surrogate decision-makers, even in competent patients
The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer:A Systematic Review and Meta-analysis of Prospective Studies
CONTEXT:Â Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies.OBJECTIVE:Â To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients.EVIDENCE ACQUISITION:Â We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators.EVIDENCE SYNTHESIS:Â We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and â„3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively.CONCLUSIONS:Â MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain.PATIENT SUMMARY:Â Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.</p
The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer:A Systematic Review and Meta-analysis of Prospective Studies
CONTEXT:Â Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies.OBJECTIVE:Â To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients.EVIDENCE ACQUISITION:Â We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators.EVIDENCE SYNTHESIS:Â We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and â„3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively.CONCLUSIONS:Â MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain.PATIENT SUMMARY:Â Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.</p
The meta-crisis of secular capitalism
The current global economic crisis concerns the way in which contemporary capitalism has turned to financialisation as a double cure for both a falling rate of profit and a deficiency of demand. Although this turning is by no means unprecedented, policies of financialisation have depressed demand (in part as a result of the long-term stagnation of average wages) while at the same time not proving adequate to restore profits and growth. This paper argues that the current crisis is less the ânormalâ one that has to do with a constitutive need to balance growth of abstract wealth with demand for concrete commodities. Rather, it marks a meta-crisis of capitalism that is to do with the difficulties of sustaining abstract growth as such. This meta-crisis is the tendency at once to abstract from the real economy of productive activities and to reduce everything to its bare materiality. By contrast with a market economy that binds material value to symbolic meaning, a capitalist economy tends to separate matter from symbol and reduce materiality to calculable numbers representing âwealthâ. Such a conception of wealth rests on the aggregation of abstract numbers that cuts out all the relational goods and the âcommonsâ on which shared prosperity depends
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Ethical principles in machine learning and artificial intelligence: cases from the field and possible ways forward
Decision-making on numerous aspects of our daily lives is being outsourced to machine-learning algorithms and artificial intelligence (AI), motivated by speed and efficiency in the decision process. Machine learning (ML) approaches - one of the typologies of algorithms underpinning artificial intelligence - are typically developed as black boxes. The implication is that ML code scripts are rarely scrutinised; interpretability is usually sacrificed in favour of usability and effectiveness. Room for improvement in practices associated with programme development have also been flagged along other dimensions, including inter alia fairness, accuracy, accountability, and transparency. In this contribution, the production of guidelines and dedicated documents around these themes is discussed. The following applications of AI-driven decision making are outlined: a) Risk assessment in the criminal justice system, and b) autonomous vehicles, highlighting points of friction across ethical principles. Possible ways forward towards the implementation of governance on AI are finally examined
How to Capitalize on the Retest Effect in Future Trials on Huntington's Disease
The retest effect-improvement of performance on second exposure to a task-may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington\u27s disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington\u27s Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in Huntington\u27s Disease (RIL-HD). All were assessed with the Unified Huntington\u27s Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1), shortly after baseline (A2) and one year later (A3). We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required
Dunno if you've any plans for the future: medical student indirect questioning in simulated oncology interviews
<p>Abstract</p> <p>Background</p> <p>This exploratory study investigated the motives of medical students (N = 63) for using indirect questions of the type <it>I don't know if </it>[you have already heard about chemotherapies], <it>I don't know how </it>[you are], or <it>I don't know what </it>[you do for a living] in simulated patient interviews during a communication skills course.</p> <p>Methods</p> <p><it>I don't know </it>questions (IDK-Qs) were observed during the initial evaluation of students' communication skills; they were systematically identified through video screening and subjected to a qualitative content and discourse analysis considering their context, their content, their intent and their effect on the simulated patients. To evaluate the specificity of medical students' IDK-Qs, the data were compared with a data set of oncologists (N = 31) conducting simulated patient interviews in the context of a Communication Skills Training (CST).</p> <p>Results</p> <p>During the interviews, 41.3% of the students asked 1-6 IDK-Qs. The IDK-Qs were attributed to three content categories: medical/treatment questions (N = 24); lifestyle/psychosocial questions (N = 18); and "inviting questions" questions (N = 11). Most of the IDK-Qs had an exploratory function (46/53), with simulated patients providing detailed responses or asking for more information (36/53). IDK-Qs were rare in the oncologist sample compared to the student sample (5 vs. 53 occurrences).</p> <p>Conclusions</p> <p>IDK-Qs showed a question design difference between medical students and oncologists in simulated patient interviews. Among other reasons for this difference, the possible function of IDK-Qs as a protective linguistic strategy and marker for psychological discomfort is discussed.</p
Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population
<div><p>Genome-wide association studies (GWAS) have identified dozens of common genetic variants associated with risk of colorectal cancer (CRC). However, the majority of CRC heritability remains unclear. In order to discover low-frequency, high-risk CRC susceptibility variants in Swedish population, we genotyped 1 515 CRC patients enriched for familial cases, and 12 108 controls. Case/control association analysis suggested eight novel variants associated with CRC risk (OR 2.0â17.6, p-value < 2.0E-07), comprised of seven coding variants in genes <i>RAB11FIP5</i>, <i>POTEA</i>, <i>COL27A1</i>, <i>MUC5B</i>, <i>PSMA8</i>, <i>MYH7B</i>, and <i>PABPC1L</i> as well as one variant downstream of <i>NEU1</i> gene. We also confirmed 27 out of 30 risk variants previously reported from GWAS in CRC with a mixed European population background. This study identified rare, coding sequence variants associated with CRC risk through analysis in a relatively homogeneous population. The segregation data suggest a complex mode of inheritance in seemingly dominant pedigrees.</p></div
Individual Liberty and the Importance of the Concept of the People
UID/FIL/00183/2013Through publically agreed laws that correspond to a common set of public restrictions, the âpeople as a sovereign bodyâ serves to protect against violations of individual liberty and despotic power. Where no such common body exists, individuals are deprived of this protection. In such cases, individuals must obey without liberty, while those in power command under a state of license. Neoliberal theorists maintain that any common personality, with its corresponding set of public and arbitrary positive and negative restrictions on liberty, undermines individual liberty. Neoliberal theory only allows for private restrictions on liberty. Against these neoliberal assumptions, we argue that rejecting public restrictions on liberty does not promote individual liberty. To the 1áą« ṏ áą áąź 1 contrary, it creates conditions in which free individuals become servile and political inequality becomes entrenched, where citizens are divided into those who obey and those who command. Tracing the consequences of neoliberalism, we argue that unless we take seriously both the people as a political category and the right to equal and reciprocal coercion, individual liberty will be at risk. We also argue that neoliberalism ultimately leads to the total exclusion of certain citizens under the veil of full liberty. With the vanishing of the peopleâs will comes the utter disappearance of certain citizens, who live in the spontaneous society as if they were stateless or lawless persons. To better understand the connections between the rejection of the concept of the people, private restrictions on liberty and the fostering of the servile citizen, this paper considers the political philosophy of Hayek and Nozick. It also considers key ideas from Locke and Kantâtheorists who, despite the differences between their philosophical perspectives, and despite the fact that they both provided crucial inspiration for Hayekâs political economy and Nozickâs libertarianism, stressed the protective role of the people with regard to individual liberty.publishersversionpublishe
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