Exploratory study of language paediatricians use to promote adherence to long-term controller medication in children with asthma

Introduction and objectives: Although patient centred communication is associated with patients’ daily medication adherence, the exact communication phenomena promoting high treatment adherence remain elusive. Patients and methods: We used conversation analysis of videotaped follow-up consultations of seven outpatients (4–13 years of age) with chronic asthma and their caregivers, consulting two paediatric respiratory physicians in a practice in which high treatment adherence has been documented, to explore the language paediatricians use to promote their patients’ adherence to daily controller medication. Results: Starting the consultation with the patient's (and caregivers’) agenda commonly resulted in presentation of issues new to the physician. Information was mostly provided in response to patient/caregiver questions, prompting the delivery of specific information tailored to the patient's and caregivers’ needs. Although patients and caregivers showed resistance in response to unsolicited information and advice, they always accepted the doctor's explicit request for agreement with proposed treatment. The doctor's description of favourable treatment results in most patients prompted caregivers’ willingness to accept treatment proposals. Conclusions: Paediatricians with a documented success in achieving adherence to controller medication in their patients with asthma tend to start consultations with the patient's agenda, provide information in response to questions, offer reassurance on overall treatment effectiveness, and seek explicit agreement with a treatment proposal

Differences in time to patient access to innovative cancer medicines in six European countries

Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: −0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: −0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe.</p

Genetically encoded photocross-linkers determine the biological binding site of exendin-4 peptide in the N-terminal domain of the intact human glucagon-like peptide-1 receptor (GLP-1R)

The glucagon-like peptide-1 receptor (GLP-1R) is a key therapeutic target in the management of type II diabetes mellitus, with actions including regulation of insulin biosynthesis and secretion, promotion of satiety, and preservation of β-cell mass. Like most class B G protein-coupled receptors (GPCRs), there is limited knowledge linking biological activity of the GLP-1R with the molecular structure of an intact, full-length, and functional receptor·ligand complex. In this study, we have utilized genetic code expansion to site-specifically incorporate the photoactive amino acid p-azido-l-phenylalanine (azF) into N-terminal residues of a full-length functional human GLP-1R in mammalian cells. UV-mediated photolysis of azF was then carried out to induce targeted photocross-linking to determine the proximity of the azido group in the mutant receptor with the peptide exendin-4. Cross-linking data were compared directly with the crystal structure of the isolated N-terminal extracellular domain of the GLP-1R in complex with exendin(9–39), revealing both similarities as well as distinct differences in the mode of interaction. Generation of a molecular model to accommodate the photocross-linking constraints highlights the potential influence of environmental conditions on the conformation of the receptor·peptide complex, including folding dynamics of the peptide and formation of dimeric and higher order oligomeric receptor multimers. These data demonstrate that crystal structures of isolated receptor regions may not give a complete reflection of peptide/receptor interactions and should be combined with additional experimental constraints to reveal peptide/receptor interactions occurring in the dynamic, native, and full-length receptor state

Design and characterization of dielectric filled TM110_{110} microwave cavities for ultrafast electron microscopy

Microwave cavities oscillating in the TM$_{110}$ mode can be used as dynamic electron-optical elements inside an electron microscope. By filling the cavity with a dielectric material it becomes more compact and power efficient, facilitating the implementation in an electron microscope. However, the incorporation of the dielectric material makes the manufacturing process more difficult. Presented here are the steps taken to characterize the dielectric material, and to reproducibly fabricate dielectric filled cavities. Also presented are two versions with improved capabilities. The first, called a dual-mode cavity, is designed to support two modes simultaneously. The second has been optimized for low power consumption. With this optimized cavity a magnetic field strength of 2.84 $\pm$ 0.07 mT was generated at an input power of 14.2 $\pm$ 0.2 W. Due to the low input powers and small dimensions, these dielectric cavities are ideal as electron-optical elements for electron microscopy setups

The Euro Diffusion Project

From 1st January 2002 we have the unique possibility to follow the spread of national euro coins over the different European countries. We model and analyse this movement and estimate the time it will take before on average half the coins in our wallet will be foreign

Does antiretroviral therapy use affect the accuracy of HIV rapid diagnostic assays? Experience from a demographic health and surveillance site in rural South Africa

Rapid diagnostic tests (RDTs) are the mainstay of HIV diagnosis in the developing world but might have poor sensitivity among individuals taking antiretroviral therapy (ART). We leveraged a home-based HIV testing program linked to clinical data to compare the sensitivity of RDTs between individuals using versus not using ART. Field workers tested 6802 individuals using 2 HIV RDTs, which were compared to a single HIV immunoassay tested on dried blood spots. Approximately 5% (371/6802) tested positive by immunoassay, of whom 157 (42%) were currently on ART. The sensitivity of the Abon RDT among those never versus currently on ART was 91.6% (95% CI 88.3–94.3) and 96.6% (95% CI 88.3–94.3), respectively, and 95.4% (95% CI 92.8–97.3) versus 99.3% (95% CI 95.2–99.7) for the Advanced Quality assay. We report similar sensitivity of RDTs in ART-naïve and ART-experienced individuals, which mitigates concerns about their use among treated individuals in population-based epidemiologic surveys and those transferring care

Human Papillomavirus and Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study regarding Tobacco and Alcohol Consumption

We aimed to determine the role of HPV in the pathogenesis and outcome of oropharyngeal squamous cell carcinoma (OSCC) in lifelong nonsmoking and nondrinking patients. A case-case analysis was performed to compare the presence of HPV-DNA in tumor cells of 16 nonsmoking and nondrinking with 16 matched smoking and drinking patients (matching criteria: age at incidence, gender, tumor sublocation, tumor stage). HPV was detected using 2 PCR tests, FISH analysis, and p16INK4A immunostaining. Nonsmoking and nondrinking patients had more HPV-positive tumors than smoking and drinking patients (n = 12; 75% versus n = 2; 13%; P < 0.001). All HPV-positive tumors showed p16INK4A overexpression, and 1 HPV-negative tumor had p16INK4A overexpression, (P < 0.001). Overall survival and disease-specific survival were higher for HPV-positive compared to HPV-negative cases (P = 0.027, P = 0.039, resp.). In conclusion, HPV is strongly associated with OSCC of nonsmoking and nondrinking patients. Specific diagnostic and therapeutic actions should be considered for these patients to achieve a better prognosis

Имитационное моделирование технологии управления процессом производства

Предложено использование комплекса имитационного моделирования для получения информации при контроле функционирования и управлении технологическим процессом производства.Запропоновано використання комплексу імітаційного моделювання для одержання інформації при контролюванні функціонування та управління технологічним процесом виробництва.Complex of simulation modeling for obtaining information when checking an operation and control of technological process of production is offered to use