Placebo and Side Effects Confound Clinical Trials on New Antitussives

This review discusses how the placebo effect related to treatment side effects may confound clinical trials on antitussives and specifically looks at the implications for trials on ATP antagonists. These new antitussives have distinctive side effects on the sensation of taste, and investigators have expressed concerns that this may unblind the clinical trials. Blinding is an essential component of trial design, but the degree of blinding in trials is rarely assessed. The assumptions of additivity and balance in clinical trials are discussed as important factors that allow assessment of the pharmacological activity of an antitussive. How side effects unbalance a clinical trial by amplifying the placebo effect of active treatments is discussed. The point is made that unblinding of trials invalidates any assessment of efficacy but that there is little interest or discussion about this fundamental aspect of trials. Proposals are discussed which may improve the blinding of trials and control placebo effects by changes to participant information, trial design, patient selection and use of active placebos. The issue of unblinding of clinical trials is not a new issue, but if real progress is to be made in developing new antitussives, then it is an issue that needs to be urgently addressed.

Flexible social learning strategies are harder than the sum of their parts

The use of ‘explicitly metacognitive’ learning strategies has been proposed as an explanation for uniquely human capacities for cumulative culture. Such strategies are proposed to rely on the use of explicit, system-2 cognitive processes, and to enable advantageous selective copying. To investigate the plausibility of this theory, we investigated participants' ability to make flexible learning decisions under executive function (EF) resource load. Over two studies adult participants completed a simple win-stay lose-shift (WSLS) paradigm task, intended to model a social learning situation where vicarious information can be used to inform response choice, by copying rewarded responses and avoiding those that are unrewarded. This was completed alongside a concurrent EF distractor task. Participants were split into three copying conditions: those that needed to use a flexible copying, WSLS strategy, those that should always copy (information trial always revealed the target), and those that should always do the opposite (information trial always revealed the non-target). The first study found significant effects of EF load and copying condition; the condition demanding a flexible strategy was more challenging than those requiring the use of one rule consistently. In addition, consistently copying was less challenging than consistently avoiding stimuli selected in the information trial. However, each information condition was equally affected by competing executive function demands. The second study found some differences between selectively copying and always copying, as well as effects of memory load, suggesting the impact of EF load on selective copying may stem from working memory requirements. No impact of EF load was found on participants’ metacognitive ability.These results suggest that learning decisions are underpinned by the use of executive functions even at a very basic level, and that selective copying strategies are more challenging than a combination of their component parts. We found minimal evidence that selective copying strategies relied on executive functions any more than consistent copying or deviation. However, task experience effects suggested that ceiling effects could be masking differences between conditions which might be apparent in other contexts. The results also suggest that such contexts might include situations in which information from a social source must be retained in memory.

Squirrel monkey responses to information from social demonstration and individual exploration using touchscreen and object choice tasks

We aimed to study whether a non-human primate species responded differently to information acquired socially compared with that acquired individually. To do so, we attempted to train squirrel monkeys to perform binary discriminations. These involved exposure to either social information (human or puppet demonstrator performs an initial ‘information trial’) or individual exploration (monkey performs information trial as well as subsequent test trials). In Experiment 1, we presented the task on a touchscreen tablet. Only one monkey appeared to learn the significance of the information trial, and across the group there was no improvement in performance over sessions. The proficient individual showed little evidence of successful transfer to three-way discrimination problems, suggesting limited representation of the task structure. In Experiment 2, we used a logically identical task, presented as a physical object choice (inverted cups concealing a food reward). No monkeys learned to use the information trial cues, and success again did not increase over sessions. We concluded that the monkeys’ poor performance in Experiment 1 was not attributable to the mode of presentation (touchscreen), but reflected real difficulties with mastering the task structure. For both experiments, we analysed the monkeys’ spontaneous responses to the different trial types (social-win, social-lose, individual-win, and individual-lose). We found that monkeys had a tendency to repeat selections made during the information trial, whether these were made by themselves or by a demonstrator. This tendency to repeat was observed even following lose trials (i.e. when incorrect). Apparent ‘success’ following win trials was probably largely an artefact of behavioural inertia (individual learning conditions) and stimulus enhancement (social learning conditions), rather than sensitivity to the reward cues associated with that stimulus. Although monkeys did respond somewhat differently (more repeats) following win trials, compared with lose trials, this was no more apparent in the object choice task than the touchscreen task, again suggesting that the less ecologically valid presentation medium did not actively disrupt potential for learning the discrimination rule. Both touchscreen and physical object choice tasks appear to be valid methods to study learning in squirrel monkeys, with neither method giving a clear performance advantage over the other. However, this population did not master the contingencies in these tasks.

Gaps in care of patients living with pulmonary fibrosis: a joint patient and expert statement on the results of a Europe-wide survey

IntroductionPulmonary fibrosis (PF) and its most common form, idiopathic pulmonary fibrosis (IPF), are chronic, progressive diseases resulting in increasing loss of lung function and impaired quality of life and survival. The aim of this joint expert and patient statement was to highlight the most pressing common unmet needs of patients with PF/IPF, putting forward recommendations to improve the quality of life and health outcomes throughout the patient journey.MethodsTwo online surveys for patients and healthcare professionals (HCPs) were conducted by the European Idiopathic Pulmonary Fibrosis and Related Disorders Federation (EU-IPFF) in 14 European countries.ResultsThe surveys were answered by 286 patients and 69 HCPs, including physicians and nurses. Delays in diagnosis and timely access to interstitial lung disease specialists and pharmacological treatment have been identified as important gaps in care. Additionally, patients and HCPs reported that a greater focus on symptom-centred management, adequate information, trial information and increasing awareness of PF/IPF is required.ConclusionsThe surveys offer important insights into the current unmet needs of PF/IPF patients. Interventions at different points of the care pathway are needed to improve patient experience.

An Analysis on the Judges’ Consideration Basis in Penalizing the Actor of Cultural Conservation Object Vandalism; Case Study in Decree of the State District of Mojokerto Number: 52/Pid.Sus/2018/PN. Mjk

The existence of ancient and cultural conservation objects are prone to damage, loss, and ruin. It is caused by either natural factor or the human’ behavior. Law enforcement against the criminals who intentionally not reporting the object presumed as Cultural Conservation Object on the Decision of the District Court of Mojokerto number: 52/Pid.Sus/2018/PN. Mjk which state that the defendant, Fendi Andriyanto Bin Badri, has been legally and conclusively proved guilty by committing crime for “intentionally not to report the findings that is presumed as a cultural conservation object and because of it, the judge sentences the defendant with 7 (seven) month of imprisonment and Rp.1000.000,- (one million rupiahs) penalty and if that penalty is not paid, it shall be substituted with 2 (two) months of imprisonment. This study was classified as a normative legal study by employing primary and the secondary data obtained from literature study. Based on the findings of the study, the basis of the judge’ consideration in subjecting the penalty was based on the aspect of certainty, fairness, and benefits of law based on the evidence materials proposed in trial, the witness’ testimony, the defendant’ testimony, the expert information, trial fact, and all the lightening and burdening things.

Retention in a Breast Cancer Risk Information Trial: Motivations of a Population-Based Sample of Women

A better understanding of factors influencing retention in breast cancer risk education and prevention programs can improve the design and effectiveness of such programs. Such information may also be useful to researchers seeking to maximize full retention in research trials involving low risk and low perceived benefit by the participants. These data are from a population-based study of 481 women from the Seattle, Washington, area, with diverse levels of breast cancer risk. This study sought to describe motivations for retention, to relate motivation variables to demographic characteristics, and to evaluate predictors of retention. Increasing age predicted study assessment completion, and both cancer worry and White ethnicity predicted intervention retention.

The Moss-Harlow Effect in Young Children: Replication

3- to 4- and 7- to 8-yr.-old children were given a series of 6-trial discrimination problems involving 2 objects after receiving either a rewarded or nonrewarded single-object information trial. During the discrimination, 2 other variables were investigated, fixed vs varying formboard position and near vs far object separation. No main effect was strong, but the age X information-trial reward condition was significant; younger Ss displayed the Moss-Harlow effect but older Ss did not. This finding supports the results of Cross and Vaughter (1966) but not those of Vaughter (1968). Other differences were anticipated on the basis of White's (1965) notions regarding a temporal learning hierarchy.