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Background This article focuses on potential strategies to support primary care researchers in working in partnership with the public and healthcare professionals. Partnership working can potentially to improve the relevance and usefulness of research and ensure better research and health outcomes.Discussion We describe what we mean by partnership working and the importance of reflecting on power and building trusting relationships. To share power in partnership working, it is essential to critically reflect on the multiple dimensions of power, their manifestations, and your own power. Power can influence relationships and therefore, it is essential to build trust with partners. Next, we outline how the context of primary care research and decisions about who you work with and how to work together, are vital considerations that are imbued with power. Lastly, we suggest different ways of working in partnership to address different dimensions of power. We provide examples from primary care research across Europe regarding how to recognise, tackle, and challenge, invisible, hidden and visible power.Conclusion We conclude by proposing three calls to actions to encourage researchers working in primary care to consider the multiple dimensions of power and move towards partnership working. First is to use participatory methods to improve the inclusivity of your research. Second is to include patients and the public in decisions about the design, delivery and development of research and its outcomes. Third is to address various systemic and institutional barriers which hinder partnership working.

ObjectiveThis study aimed to validate the newly developed composite acceptability endpoint to investigate acceptability of oral pediatric drug formulations that integrates swallowability and palatability assessments.MethodsIn this open-label study acceptability of oral formulations was tested in three age groups (1–

Abstract Background In line with the European Paediatric Regulation, the European Medicines Agency (EMA) asks for investigation of a medicine’s acceptability in paediatric medicines development. A standardised acceptability testing method combining the outcome of “swallowability” and “palatability” assessments to a “composite endpoint on acceptability” was recently developed. Before this method’s suitability for selection of the most acceptable drug formulation of a new medicine for children can be broadly recommended, the acceptance and relevance of such established acceptability needs the critical review and input from young patients with understanding of the medicines development methodology. The benefit of involving patients in drug product development, clinical research and innovation is well established. Methods During a focus group meeting with the KIDS Barcelona (young people advisory group, age 16–23 years) the suitability of the “composite endpoint on acceptability” methodology was assessed. Via electronic questionnaires the importance of involving patients in the medicines development and in the acceptability method development was investigated. Questions on how best to determine palatability and swallowability were asked. The relevance of all EMA-listed acceptability elements was assessed via coloured and numbered stickers and questionnaires. Results The results showed that the involvement of young people in the medicines and acceptability method development was rated high. The group worked out that a 5-point smiley Likert Scale is preferred for assessing acceptability by 6–11 year old patients, while a Visual Analogue Scale is preferred for collecting adolescents’ opinion. The ranking of the EMA-listed acceptability elements showed that palatability and swallowability are the most relevant parameters, while colour of the medicine was rated as least relevant. These results, established face-to-face, were confirmed in a repeat of the ranking through an electronic questionnaire, completed by the participants individually and remotely, 5 weeks later. Conclusion This work reinforced the need and value to involve young people in the medicines lifecycle, and specifically in this acceptability method development. As next step other focus group meetings with more young people from different European countries are planned.

Since the acceptability of a medicine can significantly impact therapeutic outcomes, this study aimed to determine and compare the preferences of children, parents, and healthcare professionals for the most commonly used pediatric oral medicine formulations (syrup, mini-tablets, oblong tablets, round tablets) addressing all pediatric age groups, 0–

State-of-the-art super-resolution microscopy techniques, including Stimulated Emission Depletion (STED), Reversible Saturable Optical Fluorescence Transitions (RESOLFT), and Switching Laser Mode (SLAM) microscopies, implement Laguerre-Gaussian beams, also known as vortex or doughnut beams to capture fluorescence information within a sub-wavelength area of the observed sample, effectively surpassing the diffraction limit and significantly improving the quality of the image. However, these techniques typically operate at point by point basis, involving time-consuming scanning of the sample to construct a complete, meaningful image. Therefore, for real-time live cell imaging purposes, the parallelization of illumination is crucial. In this study, we demonstrate the parallel generation of arbitrary arrays of Gaussian and Laguerre-Gaussian laser foci suitable for super-resolution microscopy. We achieve rapid scanning through the sample using acousto-optic spatial light modulation, a technique we have previously pioneered across various fields. By employing parallelized illumination with both Gaussian and doughnut beams, we aim to capture super-resolution images.

Objective: This study aimed to validate the newly developed composite acceptability endpoint to investigate acceptability of oral pediatric drug formulations that integrates swallowability and palatability assessments. Methods: In this open-label study acceptability of oral formulations was tested in three age groups (1-<6 months, 6-<12 years, and 12-<18 years) with a 2-way cross-over design in children aged 1-<6 months (syrup and mini-tablets), and with an incomplete block design of four sequences with three out of four formulations (syrup, mini-tablets, oblong tablet, and round tablet) each in children aged 6-<18 years. The primary endpoint was acceptability derived from the composite acceptability endpoint. Secondary endpoints were palatability and acceptability derived from swallowability. Results: A total of 320 children were stratified into three age groups (80 children aged 1-<6 months, 120 children aged 6-<12 years, and 120 children aged 12-<18 years). All participants completed the study. Age-specific differences were observed in acceptability derived from the composite acceptability endpoint. Mini-tablets had the highest acceptability in participants aged 1-<6 months and 6-<12 years while the oblong tablet was leading in adolescent participants (12-<18 years). Conclusion: This study demonstrated that the composite acceptability endpoint method integrating both swallowability and palatability assessments is a sensitive method to assess acceptability of drug formulations in children of different age. [ABSTRACT FROM AUTHOR]

Although drug acceptability can have a significant impact on patient adherence in pediatric therapy, data are limited, even for common therapeutic areas. We present the second part of an acceptability study conducted at the University Children’s Hospital Düsseldorf, Germany. The study investigated the acceptability of most commonly used antibiotics in a pediatric hospital setting. The researchers used the acceptability reference framework to score the acceptability of five antibiotics based on 150 real-life observer reports of medicine intake. Four antibiotics assessed in this study were formulated as preparations for injection (ampicillin, ampicillin/sulbactam, ceftriaxone, and gentamicin) and one as a powder for oral liquid suspension (co-amoxiclav). All the antibiotics formulated as preparations for injection were rated negatively due to high rates of negative reactions (80%), the use of restraint (51%), the use of extra devices (99%), and long preparation and administration times (100%). The antibiotic formulated as a powder was significantly more well accepted. The study concluded that there is a lack of appropriate formulations for antibiotics for use in children. These findings are important in improving knowledge on acceptability drivers and might help in formulating and prescribing better medicines for children. The study highlights the need for healthcare professionals to have knowledge about the acceptability of different products to select the best-adapted product for each patient.

Since the acceptability of a medicine can significantly impact therapeutic outcomes, this study aimed to determine and compare the preferences of children, parents, and healthcare professionals for the most commonly used pediatric oral medicine formulations (syrup, mini-tablets, oblong tablets, round tablets) addressing all pediatric age groups, 0–<18 years (y). This survey study employed sex-, age-, and participant group-adapted questionnaires for eight cohorts of participants, i.e., children 6–<12 y, adolescents 12–<18 y, parents of children in four age groups (0–<2 y, 2–<6 y, 6–<12 y, and 12–<18 y), nurses, and pediatricians. Descriptive statistics were used for data analysis. In the age groups 0–<2 y and 2–<6 y, mini-tablets were preferred over syrup by all participants. In the age group 6–12 y, solid dosage forms were also preferred over syrup by all participants. In the age group 12–<18 y, healthcare professionals preferred solid dosage forms over syrup. Parents preferred higher amounts of mini-tablets and syrup compared to round and oblong tablets, while adolescents' preferences did not differentiate between these formulations. Based on the study results and in contrast to current practice, it is suggested to consider solid dosage forms for future age-appropriate medicinal products already for younger age groups. [ABSTRACT FROM AUTHOR]

Mini-tablets are advantageous over liquid formulations in overcoming challenges related to stability, taste, and dosage. This open-label, single-dose, cross-over study investigated the acceptability and safety of drug-free, film-coated mini-tablets in children aged 1 month–6 years (stratified: 4–6 years, 2–

Health technology assessment (HTA) aims to be a systematic, transparent, unbiased synthesis of clinical efficacy, safety, and value of medical products (MPs) to help policymakers, payers, clinicians, and industry to make informed decisions. The evidence available for HTA has gaps—impeding timely prediction of the individual long-term effect in real clinical practice. Also, appraisal of an MP needs cross-stakeholder communication and engagement. Both aspects may benefit from extended use of modeling and simulation. Modeling is used in HTA for data-synthesis and health-economic projections. In parallel, regulatory consideration of model informed drug development (MIDD) has brought attention to mechanistic modeling techniques that could in fact be relevant for HTA. The ability to extrapolate and generate personalized predictions renders the mechanistic MIDD approaches suitable to support translation between clinical trial data into real-world evidence. In this perspective, we therefore discuss concrete examples of how mechanistic models could address HTA-related questions. We shed light on different stakeholder's contributions and needs in the appraisal phase and suggest how mechanistic modeling strategies and reporting can contribute to this effort. There are still barriers dissecting the HTA space and the clinical development space with regard to modeling: lack of an adapted model validation framework for decision-making process, inconsistent and unclear support by stakeholders, limited generalizable use cases, and absence of appropriate incentives. To address this challenge, we suggest to intensify the collaboration between competent authorities, drug developers and modelers with the aim to implement mechanistic models central in the evidence generation, synthesis, and appraisal of HTA so that the totality of mechanistic and clinical evidence can be leveraged by all relevant stakeholders.

This single-centre, open-label, randomised, parallel-group study assessed the acceptability, swallowability, palatability, and safety of film-coated, 3 mm diameter mini-tablets in children aged ≥2–

Several types of super-resolution microscopy, such as Stimulated Emission Depletion (STED), Reversible Saturable Optical Fluorescence Transitions (RESOLFT) or Switching Laser Mode (SLAM) microscopies, employ Laguerre-Gaussian beams (also called vortex or doughnut beams) to obtain fluorescence information within a sub-wavelength region of the specimen under observation, thus breaking the diffraction limit and producing images of greatly improved quality. However, in general, these techniques operate on a point-by-point basis, so we need to raster scan the sample in order to build a full, meaningful image, which takes time. Parallelization of the illumination is the only way to make these microscopies more suitable for live cell imaging applications. Here, we demonstrate the parallel production of arbitrary arrays of Gaussian and Laguerre-Gaussian lasers foci suitable for super-resolution microscopy, together with the possibility to fast scan through the sample, by means of acousto-optic spatial light modulation, a technique that we have pioneered in the past in several other fields.

Background: The European Patients' Academy on Therapeutic Innovation Switzerland (EUPATI CH) was established as an association in 2016 with the mission to improve patient empowerment in Switzerland, raise public awareness of EUPATI's education material, and foster multi-stakeholder partnerships in order to promote public involvement in all aspects of medicines research and development (R&D). In order to achieve its goal of improving patient involvement (PI) in all processes of medicines R&D in Switzerland and to obtain guidance and recommendations for future activities, EUPATI CH initiated a multi-stakeholder survey on PI experiences, hurdles, and best practices. The survey enabled EUPATI CH to obtain and analyze the views of various stakeholders and shape its workplan.Methods: Data collection occurred between January and July 2019 using a survey and semi-structured interviews with individual stakeholders from different groups. The online survey responses were analyzed using quantitative methods and the interviews were analyzed using qualitative methods.Results: The online survey was completed by 55 respondents (10%), and the semi-structured interviews were conducted with 14 stakeholders. Respondents to the online survey were patient representatives (45%), researchers from academia (25%), individuals from the pharmaceutical industry (9%), healthcare professionals (23%), and representatives from government agencies (6%). Some respondents were also members of EUPATI CH. Thirty-eight percent of respondents consider PI in Switzerland to be limited or absent. They identified the main barriers to PI as, first and foremost, a lack of funds and human resources (65%), followed by a lack of information and a lack of education on how to become a patient advocate (21%), a lack of collaboration with other stakeholders (16%), and a lack of adequate resources. Respondents' expectations of EUPATI CH's role in supporting PI were to provide education for active PI and improve networking and collaboration among stakeholders.Conclusions: EUPATI CH's multi-stakeholder research identified some of the difficulties in promoting PI in medicines R&D in Switzerland, in particular the complex collaboration among stakeholders and a lack of funds, human resources, and knowledge. To respond to these difficulties, EUPATI CH has begun preparing a basic training course for patients that is adapted to Switzerland.

The aim of this paper is to demonstrate the superior thermal performance of traditional mud architecture over contemporary concrete block construction. The case study consists of two adjacent buildings representing the two building techniques that are located in the Asiri highlands, KSA. The research employed multi-field study techniques that include observation, as well as objective and subjective assessments. The objective assessment measured the different factors affecting the thermal comfort inside the case study houses by using a data logger and handheld equipment. The subjective assessment aimed to measure the response of the occupants by using semi-structured interviews and self-directed questioners. The results will be a further stepping-stone in motivating people to find value in their heritage and to preserve, reuse and reinhabit their houses while also stressing the importance to pass traditional knowledge to younger generations. The results showed a better performance for the vernacular houses while showed significant importance of adopting the passive strategies even with the new concrete houses. Keywords: Thermal performance, Vernacular architecture, Monitoring techniques, Subjective assessment, Objective assessment, Subject classification codes: Building studies, Culture, Architecture

In order to propose a more precise definition and explore how to reduce ethical losses in randomized controlled clinical trials (RCTs), we set out to identify trial participants who do not contribute to demonstrating that the treatment in the experimental arm is superior to that in the control arm. RCTs emerged mid-last century as the gold standard for assessing efficacy, becoming the cornerstone of the value of new therapies, yet their ethical grounds are a matter of debate. We introduce the concept of unnecessary participants in RCTs, the sum of non-informative participants and non-responders. The non-informative participants are considered not informative with respect to the efficacy measured in the trial in contrast to responders who carry all the information required to conclude on the treatment's efficacy. The non-responders present the event whether or not they are treated with the experimental treatment. The unnecessary participants carry the burden of having to participate in a clinical trial without benefiting from it, which might include experiencing side effects. Thus, these unnecessary participants carry the ethical loss that is inherent to the RCT methodology. On the contrary, responders to the experimental treatment bear its entire efficacy in the RCT. Starting from the proportions observed in a real placebo-controlled trial from the literature, we carried out simulations of RCTs progressively increasing the proportion of responders up to 100%. We show that the number of unnecessary participants decreases steadily until the RCT's ethical loss reaches a minimum. In parallel, the trial sample size decreases (presumably its cost as well), although the trial's statistical power increases as shown by the increase of the chi-square comparing the event rates between the two arms. Thus, we expect that increasing the proportion of responders in RCTs would contribute to making them more ethically acceptable, with less false negative outcomes.

Angiotensin-converting enzyme inhibitors (ACEI), such as enalapril, are a cornerstone of treatment for pediatric heart failure which is still used off-label. Using a novel age-appropriate formulation of enalapril orodispersible minitablets (ODMTs), phase II/III open-label, multicenter pharmacokinetic (PK) bridging studies were performed in pediatric patients with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) in five participating European countries. Children were treated for 8 weeks with ODMTs according to an age-appropriate dosing schedule. The primary objective was to describe PK parameters (area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration (t-max)) of enalapril and its active metabolite enalaprilat. Of 102 patients, 89 patients (n = 26, DCM; n = 63 CHD) were included in the primary PK endpoint analysis. Rate and extent of enalapril and its active metabolite enalaprilat were described and etiology and age could be identified as potential PK modifying factors. The dosing schedule appeared to be tolerated well and did not result in any significant drug-related serious adverse events. The PK analysis and the lack of severe safety events supports the applied age-appropriate dosing schedule for the enalapril ODMTs.