Informed consent and placebo effects: a content analysis of information leaflets to identify what clinical trial participants are told about placebos

BackgroundPlacebo groups are used in randomised clinical trials (RCTs) to control for placebo effects, which can be large. Participants in trials can misunderstand written information particularly regarding technical aspects of trial design such as randomisation; the adequacy of written information about placebos has not been explored. We aimed to identify what participants in major RCTs in the UK are told about placebos and their effects.Methods and FindingsWe conducted a content analysis of 45 Participant Information Leaflets (PILs) using quantitative and qualitative methodologies. PILs were obtained from trials on a major registry of current UK clinical trials (the UKCRN database). Eligible leaflets were received from 44 non-commercial trials but only 1 commercial trial. The main limitation is the low response rate (13.5%), but characteristics of included trials were broadly representative of all non-commercial trials on the database. 84% of PILs were for trials with 50:50 randomisation ratios yet in almost every comparison the target treatments were prioritized over the placebos. Placebos were referred to significantly less frequently than target treatments (7 vs. 27 mentions, p<001) and were significantly less likely than target treatments to be described as triggering either beneficial effects (1 vs. 45, p<001) or adverse effects (4 vs. 39, p<001). 8 PILs (18%) explicitly stated that the placebo treatment was either undesirable or ineffective.ConclusionsPILs from recent high quality clinical trials emphasise the benefits and adverse effects of the target treatment, while largely ignoring the possible effects of the placebo. Thus they provide incomplete and at times inaccurate information about placebos. Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the fundamental rationale underpinning placebo controlled trials

Meta-learners for Estimating Heterogeneous Treatment Effects using Machine Learning

There is growing interest in estimating and analyzing heterogeneous treatment effects in experimental and observational studies. We describe a number of meta-algorithms that can take advantage of any supervised learning or regression method in machine learning and statistics to estimate the Conditional Average Treatment Effect (CATE) function. Meta-algorithms build on base algorithms---such as Random Forests (RF), Bayesian Additive Regression Trees (BART) or neural networks---to estimate the CATE, a function that the base algorithms are not designed to estimate directly. We introduce a new meta-algorithm, the X-learner, that is provably efficient when the number of units in one treatment group is much larger than in the other, and can exploit structural properties of the CATE function. For example, if the CATE function is linear and the response functions in treatment and control are Lipschitz continuous, the X-learner can still achieve the parametric rate under regularity conditions. We then introduce versions of the X-learner that use RF and BART as base learners. In extensive simulation studies, the X-learner performs favorably, although none of the meta-learners is uniformly the best. In two persuasion field experiments from political science, we demonstrate how our new X-learner can be used to target treatment regimes and to shed light on underlying mechanisms. A software package is provided that implements our methods

Papilledema in patient with primary aldosteronism. an unusual case report

Primary Aldosteronism (PA) is the most frequent form of secondary hypertension [1]. Target treatment is important to reduce the risk of cardiovascular complications. Visual field defects and papilledema are reported in PA patients

Fidelity protocol for the Action Success Knowledge (ASK) trial: A psychosocial intervention administered by speech and language therapists to prevent depression in people with post-stroke aphasia

Introduction: Treatment fidelity is a complex, multifaceted evaluative process which refers to whether a studied intervention was delivered as intended. Monitoring and enhancing fidelity is one recommendation of the TiDIER (Template for Intervention Description and Replication) checklist, as fidelity can inform interpretation and conclusions drawn about treatment effects. Despite the methodological and translational benefits, fidelity strategies have been used inconsistently within health behaviour intervention studies; in particular, within aphasia intervention studies, reporting of fidelity remains relatively rare. This paper describes the development of a fidelity protocol for the Action Success Knowledge (ASK) study, a current cluster randomised trial investigating an early mood intervention for people with aphasia (a language disability caused by stroke). Methods and analysis: A novel fidelity protocol and tool was developed to monitor and enhance fidelity within the two arms (experimental treatment and attention control) of the ASK study. The ASK fidelity protocol was developed based on the National Institutes of Health Behaviour Change Consortium fidelity framework. Ethics and dissemination: The study protocol was approved by the Darling Downs Hospital and Health Service Human Research Ethics Committee in Queensland, Australia under the National Mutual Acceptance scheme of multicentre human research projects. Specific ethics approval was obtained for those participating sites who were not under the National Mutual Agreement at the time of application. The monitoring and ongoing conduct of the research project is in line with requirements under the National Mutual Acceptance. On completion of the trial, findings from the fidelity reviews will be disseminated via publications and conference presentations. Trial registration number ACTRN12614000979651

J Inherit Metab Dis

Analysis of blood phenylalanine is central to the monitoring of patients with phenylketonuria (PKU) and age-related phenylalanine target treatment-ranges (0-12\u2009years; 120-360\u2009\u3bcmol/L, and\u2009>12\u2009years; 120-600\u2009\u3bcmol/L) are recommended in order to prevent adverse neurological outcomes. These target treatment-ranges are based upon plasma phenylalanine concentrations. However, patients are routinely monitored using dried bloodspot (DBS) specimens due to the convenience of collection. Significant differences exist between phenylalanine concentrations in plasma and DBS, with phenylalanine concentrations in DBS specimens analyzed by flow-injection analysis tandem mass spectrometry reported to be 18% to 28% lower than paired plasma concentrations analyzed using ion-exchange chromatography. DBS specimens with phenylalanine concentrations of 360 and 600\u2009\u3bcmol/L, at the critical upper-target treatment-range thresholds would be plasma equivalents of 461 and 768\u2009\u3bcmol/L, respectively, when a reported difference of 28% is taken into account. Furthermore, analytical test imprecision and bias in conjunction with pre-analytical factors such as volume and quality of blood applied to filter paper collection devices to produce DBS specimens affect the final test results. Reporting of inaccurate patient results when comparing DBS results to target treatment-ranges based on plasma concentrations, together with inter-laboratory imprecision could have a significant impact on patient management resulting in inappropriate dietary change and potentially adverse patient outcomes. This review is intended to provide perspective on the issues related to the measurement of phenylalanine in blood specimens and to provide direction for the future needs of PKU patients to ensure reliable monitoring of metabolic control using the target treatment-ranges.CC999999/ImCDC/Intramural CDC HHS/United States2021-03-15T00:00:00Z31433494PMC7957320930

Flexible Recording/High Energy Electrode Catheter with Anchor for Ablation of Atrial Flutter by Radio Frequency Energy

An electrode catheter is provided having a predetermined flexibility throughout the entire length or at least at the contact portion, such as the electrode region, to allow for the molding of the contact portion such that it conforms to the shape of the heart at a preselected desired target area, such as the isthmus between the inlet of inferior vena cava and posterior tricuspid annulus. The catheter also includes a guiding sheath that is preferably semirigid and may be pre-shaped with at least one bend or angulation to assist in molding to ensure that the electrode region overlies the desired target treatment area. A remotely controlled anchoring device is provided at the distal end of the catheter for anchoring it in position to facilitate the molding operation and placement over the target treatment area. A method of cardiac ablation using the catheter of the present invention is also disclosed

Multi-target treatment of bone cancer pain using synergistic combinations of pharmacological compounds in experimental animals

Non peer reviewe

Vegetation and the importance of insecticide-treated target siting for control of Glossina fuscipes fuscipes

Control of tsetse flies using insecticide-treated targets is often hampered by vegetation re-growth and encroachment which obscures a target and renders it less effective. Potentially this is of particular concern for the newly developed small targets (0.25 high × 0.5 m wide) which show promise for cost-efficient control of Palpalis group tsetse flies. Consequently the performance of a small target was investigated for Glossina fuscipes fuscipes in Kenya, when the target was obscured following the placement of vegetation to simulate various degrees of natural bush encroachment. Catches decreased significantly only when the target was obscured by more than 80%. Even if a small target is underneath a very low overhanging bush (0.5 m above ground), the numbers of G. f. fuscipes decreased by only about 30% compared to a target in the open. We show that the efficiency of the small targets, even in small (1 m diameter) clearings, is largely uncompromised by vegetation re-growth because G. f. fuscipes readily enter between and under vegetation. The essential characteristic is that there should be some openings between vegetation. This implies that for this important vector of HAT, and possibly other Palpalis group flies, a smaller initial clearance zone around targets can be made and longer interval between site maintenance visits is possible both of which will result in cost savings for large scale operations. We also investigated and discuss other site features e.g. large solid objects and position in relation to the water's edge in terms of the efficacy of the small targets