What crowding can tell us about object representations.

In crowding, perception of a target usually deteriorates when flanking elements are presented next to the target. Surprisingly, adding further flankers can lead to a release from crowding. In previous work we showed that, for example, vernier offset discrimination at 9° of eccentricity deteriorated when a vernier was embedded in a square. Adding further squares improved performance. The more squares presented, the better the performance, extending across 20° of the visual field. Here, we show that very similar results hold true for shapes other than squares, including unfamiliar, irregular shapes. Hence, uncrowding is not restricted to simple and familiar shapes. Our results provoke the question of whether any type of shape is represented at any location in the visual field. Moreover, small changes in the orientation of the flanking shapes led to strong increases in crowding strength. Hence, highly specific shape-specific interactions across large parts of the visual field determine vernier acuity.

Prevalence of Polypharmacy and Inappropriate Medication in Adults With Intellectual Disabilities in a Hospital Setting in Switzerland.

Background: Polypharmacy and inappropriate prescription are frequent in vulnerable and multi-morbid populations. Adults with intellectual disability (ID) are at risk of being polymedicated because they often present with multiple comorbidities and challenging behaviors. Aim: The objective of this study was thus to evaluate the prevalence of potentially inappropriate medications (PIM) and polypharmacy in a hospital unit dedicated to adults with ID. Methods: A 10-month prospective observational study took place at a hospital unit specializing in the care of adults with ID in Geneva, Switzerland. Once a week, health and prescription data were collected and screened for PIM according to preset definitions. Results: Fourteen patients consented to participate, leading to 20 hospitalization events assessed during the study. Hospitalizations lasted 12.8 weeks on average. ID severities ranged from mild to profound, all degrees of severity being equally represented. One hundred percent of the patients were polymedicated (defined as five drugs or more prescribed simultaneously). A mean number of 9.4 drugs were prescribed per week, including 5.3 psychotropic drugs. The number of prescribed drugs remained stable throughout the hospitalizations. Antipsychotics were the most prescribed drug class (19% of all prescribed drugs), followed by benzodiazepines (13%) and laxatives (12%). A total of 114 PIM were recorded with an average of 5.7 PIM per hospitalization. Conclusions: This study showed that polypharmacy and inappropriate prescription are very common in adults with ID, even though the literature and expert positions advocate for deprescription in these patients. Specific prescribing and deprescribing guidelines are needed for that specific population.

TOP-ID: a Delphi technique-guided development of a prescription and deprescription tool for adults with intellectual disabilities.

OBJECTIVES: Adults with an intellectual disability (AWID) are often polymedicated because of somatic and psychiatric health problems. Besides, they may display challenging behaviours, leading to off-label prescription of psychotropic drugs, without efficacy and with numerous adverse effects. In this context, a prescription/deprescription tool (Tool for Optimising Prescription in Intellectual Disability/TOP-ID) was developed to improve the care of AWID. This paper describes how TOP-ID was designed. DESIGN: Four-step consensus-based process involving a review of the literature, eight semistructured interviews and a two-round Delphi process. SETTING: Seventeen general practices and university and general hospitals from Belgium, France and Switzerland. PARTICIPANTS: Eighteen French-speaking physicians from different domains of expertise participated in the Delphi process. PRIMARY AND SECONDARY OUTCOME MEASURES: For the Delphi iteration process, consensus was defined as at least a 65% agreement between the experts. RESULTS: Two rounds were needed for the Delphi process. Eighty-one items of the tool were submitted to 18 out of 35 recruited French-speaking experts during the first round. Sixty-nine per cent of the items reached a rate of agreement of 65% or more in that round. Thirteen questions were reformulated and resubmitted for the second Delphi iteration round. All of the statements reached a rate of agreement of 65% or more in the second round. CONCLUSION: TOP-ID is the first prescription-deprescription tool developed specifically for AWIDs in French. It is intended to help prescribers document patient care in order to reduce prescription errors and to improve safety. The next steps of the project include the development of an electronic version of TOP-ID and a utility study.

Pain interventions in adults with intellectual disability: A scoping review and pharmacological considerations.

BACKGROUND AND OBJECTIVE: Having to deal on a daily routine with prescriptions in adults with intellectual disability (ID), we systematically reviewed the literature on the specificities of pain interventions in that population, focusing on medication and trying to gather practical information on appropriate pain treatments. Given the scarcity of the literature on the topic, we also discussed the pharmacological considerations to be taken into account when prescribing analgesic drugs in that vulnerable population. DATABASES AND DATA TREATMENT: Articles on pain and ID were searched in the Medline and Google scholar electronic databases using the key words "Intellectual Disability," "Developmental Disability" and specific keywords for pharmacological and non-pharmacological pain interventions. Preset outcomes about pharmacological treatment specificity, efficacy and safety were then collected. RESULTS: One hundred and fifty-two articles were found and 16 were retained based on our inclusion and exclusion criteria. Of the 16 articles, five were topical reviews. Among the 11 remaining articles, five discussed pharmacological interventions, four considered non-pharmacological interventions and two discussed both. As anticipated, the literature matching our specific outcomes about the pharmacological treatment of pain was scarce and for the most part not designed to answer the questions of specificity, efficacy and safety of pain treatment in adults with ID. CONCLUSION: The specificity of analgesic treatments in adults with ID is a totally unexplored domain. In the absence of clinical guidelines, pharmacological facts-such as inter-individual variability in drug response, pharmacokinetic and pharmacodynamic interactions, frequent co-morbidities and ease of administration-must be systematically integrated, when prescribing in the population of adults with ID. SIGNIFICANCE: This review synthesizes the state of research on pain interventions in adults with ID and is one of the rare articles addressing the specificities of analgesic prescriptions in this population.

Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study.

BACKGROUND: The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z). METHODS: We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18-65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 × 10(10) viral particles), low-dose vaccine (2·5 × 10(10) viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02289027. FINDINGS: Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low-dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola glycoprotein peaked on day 28 at 51 µg/mL (95% CI 41·1-63·3) in the high-dose group, 44·9 µg/mL (25·8-56·3) in the low-dose group, and 5·2 µg/mL (3·5-7·6) in the placebo group, with respective response rates of 96% (95% CI 85·7-99·5), 96% (86·5-99·5), and 5% (0·1-24·9). Geometric mean concentrations decreased by day 180 to 25·5 µg/mL (95% CI 20·6-31·5) in the high-dose group, 22·1 µg/mL (19·3-28·6) in the low-dose group, and 3·2 µg/mL (2·4-4·9) in the placebo group. 28 (57%) participants given high-dose vaccine and 31 (61%) participants given low-dose vaccine developed glycoprotein-specific CD4 cell responses, and 33 (67%) and 35 (69%), respectively, developed CD8 responses. INTERPRETATION: ChAd3-EBO-Z was safe and well tolerated, although mild to moderate systemic adverse events were common. A single dose was immunogenic in almost all vaccine recipients. Antibody responses were still significantly present at 6 months. There was no significant difference between doses for safety and immunogenicity outcomes. This acceptable safety profile provides a reliable basis to proceed with phase 2 and phase 3 efficacy trials in Africa. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), through the EU Horizon 2020 Research and Innovation Programme.