Institutional use of National Clinical Audits by healthcare providers

Rationale, aims, and objectives Healthcare systems worldwide devote significant resources towards collecting data to support care quality assurance and improvement. In the United Kingdom, National Clinical Audits are intended to contribute to these objectives by providing public reports of data on healthcare treatment and outcomes, but their potential for quality improvement in particular is not realized fully among healthcare providers. Here, we aim to explore this outcome from the perspective of hospital boards and their quality committees: an under‐studied area, given the emphasis in previous research on the audits' use by clinical teams. Methods We carried out semi‐structured, qualitative interviews with 54 staff in different clinical and management settings in five English National Health Service hospitals about their use of NCA data, and the circumstances that supported or constrained such use. We used Framework Analysis to identify themes within their responses. Results We found that members and officers of hospitals' governing bodies perceived an imbalance between the benefits to their institutions from National Clinical Audits and the substantial resources consumed by participating in them. This led some to question the audits' legitimacy, which could limit scope for improvements based on audit data, proposed by clinical teams. Conclusions Measures to enhance the audits' perceived legitimacy could help address these limitations. These include audit suppliers moving from an emphasis on cumulative, retrospective reports to real‐time reporting, clearly presenting the “headline” outcomes important to institutional bodies and staff. Measures may also include further negotiation between hospitals, suppliers and their commissioners about the nature and volume of data the latter are expected to collect; wider use by hospitals of routine clinical data to populate audit data fields; and further development of interactive digital technologies to help staff explore and report audit data in meaningful ways

Light-Dependent Changes in the Spatial Localization of Metabolites in Solenostemon scutellarioides (Coleus Henna) Visualized by Matrix-Free Atmospheric Pressure Electrospray Laser Desorption Ionization Mass Spectrometry Imaging

The visualization of foliage color in plants provides immediate insight into some of the compounds that exist in the leaf. However, many non-colored compounds are also present; their cellular distributions are not readily identifiable optically. In this study we evaluate the applicability of mass spectrometry imaging (MSI) via electrospray laser desorption ionization (ELDI) to reveal the spatial distribution of metabolites. ELDI-MSI is a matrix free, atmospheric pressure ionization method that utilizes a UV laser coupled with supplemental ionization by electrospray. We specifically applied ELDI-MSI to determine the spatial distribution of metabolites in Coleus Henna half leaves that were grown with half-sections either fully illuminated or shaded. We monitored dynamic changes in the spatial distribution of metabolites in response to the change of illumination every 7 days for a 28 day period. A novel source-sink relationship was observed between the 2 halves of the experimental leaf. Furthermore, Coleus Henna leaves present visually recognizable sectors associated with the differential accumulation of flavonoids. Thus, we correlated the effect of differential illumination and presence or absence of flavonoids with metabolic changes revealed by the accumulation of carbohydrates, amino acids, and organic acids. The results show the potential of ELDI-MSI to provide spatial information for a variety of plant metabolites with little sample preparation

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Diagnosis of Agglomeration and Crystallinity of Active Pharmaceutical Ingredients in Over the Counter Headache Medication by Electrospray Laser Desorption Ionization Mass Spectrometry Imaging

Agglomeration of active pharmaceutical ingredients (API) in tablets can lead to decreased bioavailability in some enabling formulations. In a previous study, we determined that crystalline APIs can be detected as agglomeration in tablets formulated with amorphous acetaminophen tablets. Multiple method advancements are presented to better resolve agglomeration caused by crystallinity in standard tablets. In this study, we also evaluate three “budget” over-the-counter headache medications (subsequently labeled as brands A, B, and C) for agglomeration of the three APIs in the formulation: Acetaminophen, aspirin, and caffeine. Electrospray laser desorption ionization mass spectrometry imaging (ELDI-MSI) was used to diagnose agglomeration in the tablets by creating molecular images and observing the spatial distributions of the APIs. Brand A had virtually no agglomeration or clustering of the active ingredients. Brand B had extensive clustering of aspirin and caffeine, but acetaminophen was observed in near equal abundance across the tablet. Brand C also had extensive clustering of aspirin and caffeine, and minor clustering of acetaminophen. These results show that agglomeration with active ingredients in over-the-counter tablets can be simultaneously detected using ELDI-MS imaging

Characteristics of de novo structural changes in the human genome

Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de novo structural changes identified in whole genomes of 250 families, including complex indels, retrotransposon insertions, and interchromosomal events. These data indicate a mutation rate of 2.94 indels (120 bp) and 0.16 SVs (>20 bp) per generation. De novo structural changes affect on average 4.1 kbp of genomic sequence and 29 coding bases per generation, which is 91 and 52 times more nucleotides than de novo substitutions, respectively. This contrasts with the equal genomic footprint of inherited SVs and substitutions. An excess of structural changes originated on paternal haplotypes. Additionally, we observed a nonuniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations