Estriol serum levels in new and chronic users of vaginal estriol cream: A prospective observational study.

AIMS: To quantify estriol serum concentrations in "new" and "chronic users" of topical estriol cream using quantitative liquid chromatography tandem mass spectrometry. METHODS: In this singlecentre prospective observational study, postmenopausal women with urogynaecological complaints were enrolled: 40 had not used topical estriol previously ("new users") and 50 had been applying estriol cream for more than 12 weeks ("chronic users"). In "new users," serum estriol levels were measured at baseline and after 12 weeks use. Estriol cream 1 mg/g was used daily for 3 weeks, then twice weekly with applicator (group 1A) or digitally (group 1B) or three times per week digitally (group 1C). "Chronic users" applied the cream twice (n = 7) or three (n = 43) times per week. Serum samples were taken in the morning after using cream the previous night. The main outcome measures were estriol serum concentrations in "new" and "chronic users" of estriol cream. RESULTS: Baseline serum estriol concentrations were less than 5 pmol/L in all 40 "new users." At 12 weeks, the 12-hour serum estriol levels ranged from less than 5 to 494 pmol/L (median 22.8; Interquartile range [IQR] 9.2-108.5). Seven "new users" had levels more than 100 pmol/L. Most of the 50 "chronic users" also had 12-hour levels less than 100 pmol/L (median 15.1 pmol/L [IQR 2.7-33.9]: three had levels more than 100 pmol/L. CONCLUSIONS: This study reports serum estriol concentrations in a large number of "new" and "chronic users" of vaginal estriol cream, employing a novel highly sensitive and specific technique. Overall, the results are reassuring: 87% had 12-hour estriol levels less than 100 pmol/L.

2022 White Paper on Recent Issues in Bioanalysis: Enzyme Assay Validation, BAV for Primary End Points, Vaccine Functional Assays, Cytometry in Tissue, LBA in Rare Matrices, Complex NAb Assays, Spectral Cytometry, Endogenous Analytes, Extracellular Vesicles Part 2 - Recommendations on Biomarkers/CDx, Flow Cytometry, Ligand-Binding Assays Development & Validation; Emerging Technologies; Critical Reagents Deep Characterization.

The 16th Workshop on Recent Issues in Bioanalysis (16th WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on LBA, Biomarkers/CDx and Cytometry. Part 1 (Mass Spectrometry and ICH M10) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 15 of Bioanalysis, issues 16 and 14 (2023), respectively.

Key Stakeholder Barriers and Facilitators to Implementing Remote Monitoring Technologies: Protocol for a Mixed Methods Analysis.

BACKGROUND: The implementation of novel digital solutions within the National Health Service has historically been challenging. Since the start of the COVID-19 pandemic, there has been a greater push for digitization and for operating remote monitoring solutions. However, the implementation and widespread adoption of this type of innovation have been poorly studied. OBJECTIVE: We aim to investigate key stakeholder barriers and facilitators to implementing remote monitoring solutions to identify factors that could affect successful adoption. METHODS: A mixed methods approach will be implemented. Semistructured interviews will be conducted with high-level stakeholders from industry and academia and health care providers who have played an instrumental role in, and have prior experience with, implementing digital solutions, alongside the use of an adapted version of the Technology Acceptance Model questionnaire. RESULTS: Enrollment is currently underway, having started in February 2022. It is anticipated to end in July 2022, with data analysis scheduled to commence in August 2022. CONCLUSIONS: The results of our study may highlight key barriers and facilitators to implementing digital remote monitoring solutions, thereby allowing for improved widespread adoption within the National Health Service in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT05321004; https://clinicaltrials.gov/ct2/show/NCT05321004.

Outcomes of Vital Sign Monitoring of an Acute Surgical Cohort With Wearable Sensors and Digital Alerting Systems: A Pragmatically Designed Cohort Study and Propensity-Matched Analysis.

Background: The implementation and efficacy of wearable sensors and alerting systems in acute secondary care have been poorly described. Objectives: to pragmatically test one such system and its influence on clinical outcomes in an acute surgical cohort. Methods: In this pragmatically designed, pre-post implementation trial, participants admitted to the acute surgical unit at our institution were recruited. In the pre-implementation phase (September 2017 to May 2019), the SensiumVitals™ monitoring system, which continuously measures temperature, heart, and respiratory rates, was used for monitoring alongside usual care (intermittent monitoring in accordance with the National Early Warning Score 2 [NEWS 2] protocol) without alerts being generated. In the post-implementation phase (May 2019 to March 2020), alerts were generated when pre-established thresholds for vital parameters were breached, requiring acknowledgement from healthcare staff on provided mobile devices. Hospital length of stay, intensive care use, and 28-days mortality were measured. Balanced cohorts were created with 1:1 'optimal' propensity score logistic regression models. Results: The 1:1 matching method matched the post-implementation group (n = 141) with the same number of subjects from the pre-implementation group (n = 141). The median age of the entire cohort was 52 (range: 18-95) years and the median duration of wearing the sensor was 1.3 (interquartile range: 0.7-2.0) days. The median alert acknowledgement time was 111 (range: 1-2,146) minutes. There were no significant differences in critical care admission (planned or unplanned), hospital length of stay, or mortality. Conclusion: This study offered insight into the implementation of digital health technologies within our institution. Further work is required for optimisation of digital workflows, particularly given their more favourable acceptability in the post pandemic era. Clinical trials registration information: ClinicalTrials.gov Identifier: NCT04638738.

Raising the bar. Interview by Sue Learner.

As part of a quality management programme at one trust every ward is ranked on 15 standards and the results are published.

Exploiting Single Domain Antibodies as Regulatory Parts to Modulate Monoterpenoid Production in E. coli.

Synthetic biology and metabolic engineering offer potentially green and attractive routes to the production of high value compounds. The provision of high-quality parts and pathways is crucial in enabling the biosynthesis of chemicals using synthetic biology. While a number of regulatory parts that provide control at the transcriptional and translational level have been developed, relatively few exist at the protein level. Single domain antibodies (sdAb) such as camelid heavy chain variable fragments (VHH) possess binding characteristics which could be exploited for their development and use as novel parts for regulating metabolic pathways at the protein level in microbial cell factories. Here, a platform for the use of VHH as tools in Escherichia coli is developed and subsequently used to modulate linalool production in E. coli. The coproduction of a Design of Experiments (DoE) optimized pBbE8k His6-VHHCyDisCo system alongside a heterologous linalool production pathway facilitated the identification of anti-bLinS VHH that functioned as modulators of bLinS. This resulted in altered product profiles and significant variation in the titers of linalool, geraniol, nerolidol, and indole obtained. The ability to alter the production levels of high value terpenoids, such as linalool, in a tunable manner at the protein level could represent a significant step forward for the development of improved microbial cell factories. This study serves as a proof of principle indicating that VHH can be used to modulate enzyme activity in engineered pathways within E. coli. Given their almost limitless binding potential, we posit that single domain antibodies could emerge as powerful regulatory parts in synthetic biology applications.

Triangle of prevention: a union's experience promoting a systems-of-safety health and safety program.

After years of watching company health and safety programs fail to prevent major incidents, injuries, illness, and death in industrial workplaces, union health and safety staff and rank and file activists took up the challenge of creating a union-run alternative program. Named the Triangle of Prevention (TOP), the program successfully engages both local unions and management in incident and near-miss reporting and investigation, root cause analysis, recommending and tracking solutions, and learning and sharing lessons. In all phases, TOP uses a hierarchical, systems-of-safety-based approach to hazard identification, reporting, prevention and control while aiming to engage the union, its members, and all other employees of a worksite. This article explains the foundations and workings of this program, the role of an expansive worker-to-worker training regimen, and the ways in which the program has transformed workplaces.

Beyond Texas City: the state of process safety in the unionized U.S. oil refining industry.

The March 2005 British Petroleum (BP) Texas City Refinery disaster provided a stimulus to examine the state of process safety in the U.S. refining industry. Participatory action researchers conducted a nation-wide mail-back survey of United Steelworkers local unions and collected data from 51 unionized refineries. The study examined the prevalence of highly hazardous conditions key to the Texas City disaster, refinery actions to address those conditions, emergency preparedness and response, process safety systems, and worker training. Findings indicate that the key highly hazardous conditions were pervasive and often resulted in incidents or near-misses. Respondents reported worker training was insufficient and less than a third characterized their refineries as very prepared to respond safely to a hazardous materials emergency. The authors conclude that the potential for future disasters plagues the refining industry. In response, they call for effective proactive OSHA regulation and outline ten urgent and critical actions to improve refinery process safety.