Maintaining the quality of vaccines through the use of standards: Current challenges and future opportunities.

An international hybrid meeting held 21-22 June 2023 in Ottawa, Canada brought together regulators, scientists, and industry experts to discuss a set of principles and best practices in the development and implementation of standards. Although the use of international standards (ISs) and international units (IUs) has been an essential part of ensuring human and animal vaccine quality in the past decades, the types and uses of standards have expanded with technological advances in manufacture and testing of vaccines. The needs of stakeholders are evolving in response to the ever-increasing complexity, diversity, and number of vaccine products as well as increasing efforts to replace animal-based potency tests with in vitro assays that measure relevant quality attributes. As such, there must be a concomitant evolution in the design and implementation of both international and in-house standards. Concomitantly, greater harmonization of regulatory expectations must be achieved through collaboration with standard-setting organizations, national control laboratories and manufacturers. Stakeholders provided perspectives on challenges and several recommendations emerged as essential to advancing agreed upon objectives.

The role community-based healthcare providers play in managing hard-to-heal wounds.

It is common for community-based healthcare providers (CHPs)-many of whom have not received specialised training in wound care-to deliver initial and ongoing management for various wound types and diverse populations. Wounds in any setting can rapidly transition to a stalled, hard-to-heal wound (HTHW) that is not following a normal healing trajectory. Failure to recognise or address issues that cause delayed healing can lead to increased costs, healthcare utilisation and suffering. To encourage early intervention by CHPs, a panel of wound care experts developed actionable evidence-based recommendations for CHPs delineating characteristics and appropriate care in identifying and treating HTHWs. A HTHW is a wound that fails to progress towards healing with standard therapy in an orderly and timely manner and should be referred to a qualified wound care provider (QWCP) for advanced assessment and diagnosis if not healed or reduced in size by 40%-50% within 4 weeks. HTHWs occur in patients with multiple comorbidities, and display increases in exudate, infection, devitalised tissue, maceration or pain, or no change in wound size. CHPs can play an important initial role by seeing the individual's HTHW risk, addressing local infection and providing an optimal wound environment. An easy-to-follow one-page table was developed for the CHP to systematically identify, evaluate and treat HTHWs, incorporating a basic toolkit with items easily obtainable in common office/clinic practice settings. A flow chart using visual HTHW clinical cues is also presented to address CHPs with different learning styles. These tools encourage delivery of appropriate early interventions that can improve overall healthcare efficiency and cost.

3Rs implementation in veterinary vaccine batch-release testing: Current state-of-the-art and future opportunities. A webinar and workshop report.

Regulatory authorities require veterinary batch-release testing to confirm vaccine potency and safety, but these tests have traditionally relied on large numbers of laboratory animals. Advances in vaccine research and development offer increasing opportunities to replace in vivo testing, and some stakeholders have made significant progress in incorporating 3Rs elements in quality control strategies. A three-part event series entitled "3Rs Implementation in Veterinary Vaccine Batch-Release Testing: Current state-of-the-art and future opportunities" was jointly organized by the Animal-Free Safety Assessment Collaboration, HealthforAnimals, and the International Alliance of Biological Standardization. Two webinars and a workshop aimed to outline the state-of-the-art non-animal approaches for veterinary batch-release testing. The events included information on the state of the deletion of obsolete safety testing and the current initiatives implemented by European, North American, and Asian-Pacific stakeholders on 3Rs implementation and regulatory acceptance. The events contributed to a better understanding of the barriers to 3Rs implementation. Participants highlighted the need for open communication, continued collaboration between stakeholders, and international harmonization of regulatory requirements to help accelerate acceptance. Despite the challenges, the countries represented at this three-part event have shared their commitments to advancing the acceptance of alternative methods.

Factors influencing Scottish dairy farmers' antibiotic use.

BACKGROUND: Good stewardship of antibiotics can reduce the development and impact of antimicrobial resistance (AMR); therefore, understanding farmers' antibiotic use is of interest to stakeholders. To date, few qualitative studies have looked at farmers' antibiotic use on dairy farms in the UK. METHODS: Semi-structured interviews were used to explore 15 Scottish dairy farmers' antibiotic use behaviours and the factors influencing their antibiotic use on farms. RESULTS: Using an inductive process, the results from the interviews were analysed, and four key themes were extracted: use of antibiotics, awareness of AMR, determinants of antibiotic use and future aspirations. LIMITATIONS: Some of the farmers interviewed were wary about discussing their antibiotic use, which could mean that some contentious issues were not discussed. The farmers also all belonged to a single milk-buying group, which may limit the generalisability of the findings. CONCLUSIONS: The quantities of antibiotics used were felt to be driven by the disease prevalence on farms, cows being indoors more, increasing herd sizes resulting in increased stocking densities, retention of poorer cows and substandard housing. Farmer knowledge of antibiotics varied, and not all farmers interviewed were aware of AMR. The farm veterinarian, the press and peers were found to be the main sources of antibiotic information.

Best practice for wound repair and regeneration use of cellular, acellular and matrix-like products (CAMPs).

There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.

The Temporal Dynamics of Brain-to-Brain Synchrony Between Students and Teachers Predict Learning Outcomes.

Much of human learning happens through interaction with other people, but little is known about how this process is reflected in the brains of students and teachers. Here, we concurrently recorded electroencephalography (EEG) data from nine groups, each of which contained four students and a teacher. All participants were young adults from the northeast United States. Alpha-band (8-12 Hz) brain-to-brain synchrony between students predicted both immediate and delayed posttest performance. Further, brain-to-brain synchrony was higher in specific lecture segments associated with questions that students answered correctly. Brain-to-brain synchrony between students and teachers predicted learning outcomes at an approximately 300-ms lag in the students' brain activity relative to the teacher's brain activity, which is consistent with the time course of spoken-language comprehension. These findings provide key new evidence for the importance of collecting brain data simultaneously from groups of learners in ecologically valid settings.

Independent control of COVID-19 vaccines by EU Official Control Authority Batch Release: challenges, strengths and successes.

Vaccines have been a key tool in stemming the tide of the COVID-19 pandemic. The rapid development of effective vaccines against COVID-19, together with their regulatory approval and wide scale distribution has been achieved in an impressively short period thanks to the intense efforts of many. In parallel to vaccine development, the EU considered it important to prepare for the independent control of the COVID-19 vaccines, including testing, to help ensure that only vaccines that comply with the approved quality requirements reach the public and to help improve/increase public confidence in the vaccines. The existing EU Official Control Authority Batch Release (OCABR) system, co-ordinated by the European Directorate for the Quality of Medicines and HealthCare (EDQM), was able to effectively respond to the need, through rapid co-ordination, work-sharing, advance planning and early interaction with manufacturers, the Coalition for Epidemic Preparedness Innovation (CEPI) and regulatory authorities. The Official Medicines Control Laboratories (OMCLs) involved in the OCABR activity, using the strength of the established system in the OCABR network and adaptations to the crisis conditions, were ready to release the first COVID-19 vaccine batches, after protocol review and testing, at the time of the conditional marketing authorisation for each of the COVID-19 vaccines, with no delay for batches reaching the public. Thanks to the dedication of resources by the EU and national authorities as well as by the EDQM, this was done without impacting the release of the other vaccines and human blood and plasma derived medicinal products, essential for public health. Transparency and communication of practices were important factors to support reliance on the OCABR outcome in non-EU countries, with the goal to improve access to vaccines in Europe and beyond. An overview of the process, legal background, challenges and successes of OCABR for COVID-19 vaccines as well as a look at the international perspective and lessons learned is provided.

LidocAine Versus Opioids In MyocarDial infarction: the AVOID-2 randomized controlled trial.

AIMS: Opioid analgesia has been shown to interfere with the bioavailability of oral P2Y12 inhibitors prompting the search for safe and effective non-opioid analgesics to treat ischaemic chest pain. METHODS AND RESULTS: The lidocAine Versus Opioids In MyocarDial infarction trial was a prospective, Phase II, prehospital, open-label, non-inferiority, randomized controlled trial enrolling patients with suspected STEACS with moderate to severe pain [numerical rating scale (NRS) at least 5/10]. Intravenous lidocaine (maximum dose 300 mg) or intravenous fentanyl (up to 50 µg every 5 min) were administered as prehospital analgesia. The co-primary end points were prehospital pain reduction and adverse events requiring intervention. Secondary end points included peak cardiac troponin I, cardiac MRI (cMRI) assessed myocardial infarct size and clinical outcomes to 30 days. A total of 308 patients were enrolled. The median reduction in pain score (NRS) was 4 vs. 3 in the fentanyl and lidocaine arms, respectively, for the primary efficacy end point [estimated median difference -1 (95% confidence interval -1.58, -0.42, P = 0.5 for non-inferiority, P = 0.001 for inferiority of lidocaine)]. Adverse events requiring intervention occurred in 49% vs. 36% of the fentanyl and lidocaine arms which met non-inferiority and superiority favouring lidocaine (P = 0.016 for superiority). No significant differences in myocardial infarct size and clinical outcomes at 30 days were seen. CONCLUSION: IV Lidocaine did not meet the criteria for non-inferiority with lower prehospital pain reduction than fentanyl but was safe and better tolerated as analgesia in ST-elevation myocardial infarction (STEMI). Future trials testing non-opioid analgesics in STEMI and whether opioid avoidance improves clinical outcomes are needed. TRIAL REGISTRATION: CTRN12619001521112p.

Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps. A workshop Report.

This online workshop Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps was organized on October 14th, 2021, by the Animal Free Safety Assessment Collaboration (AFSA), the Humane Society International (HSI), the European Federation of Pharmaceutical Industries and Associations (EFPIA), in collaboration with the International Alliance of Biological Standardization (IABS). The workshop saw a participation of over a hundred representatives from international organizations, pharmaceutical industries and associations, and regulatory authorities of 28 countries. Participants reported on country- and region-specific regulatory requirements and, where present, on the perspectives on the waiving and elimination of the Abnormal Toxicity Test. With AFSA, HSI, EFPIA and IABS representatives as facilitators, the participants also discussed specific country/global actions to further secure the deletion of ATT from all regulatory requirements worldwide.

Bid from the Association for the Advancement of Wound Care.

The Association for the Advancement of Wound Care sets out its bid for the WUWHS 2026 Congress to be held in Chicago, Illinois, US.

Determining the influence of socio-psychological factors on the adoption of individual 'best practice' parasite control behaviours from Scottish sheep farmers.

Since 2003, the Sustainable Control Of Parasites in Sheep (SCOPS) group have provided the UK sheep farming industry with guidance on ways to mitigate the development and dissemination of anthelmintic resistance (AR). However our empirical understanding of sheep farmers' influences towards such 'best practice' parasite control approaches is limited, and therefore requires further assessment and evaluation to identify the potential factors influencing their implementation. In 2015, a telephone questionnaire was conducted in order to elicit Scottish sheep farmers' attitudes and behaviours regarding the SCOPS recommended practices, as well as gauging farmers' general attitudes to gastrointestinal nematodes (GIN; term roundworm used in questionnaire) control. A quantitative structural equation modelling (SEM) approach was employed to determine the influences of socio-psychological factors and the uptake of individual anthelmintic resistance mitigating practices including: the implementation of a quarantine strategy for parasite control and the use of parasite diagnostic testing for monitoring faecal egg counts (FEC) and detecting AR. The proposed models established a good fit with the observed data and explained 61%, 54% and 27% of the variance in the adoption of AR testing, FEC monitoring, and quarantine behaviours respectively. The results presented highlight a number of consistent and distinct factors significantly influencing the implementation of selected SCOPS recommended practices. The negative influences of topography and farmer experience was frequently demonstrated in relation to multiple GIN control practices, as well as the positive influences of social norms, worm control knowledge, AR risk perception and positive attitudes to the services provided by the veterinary profession. Factors that were shown to have the greatest relative effects on individual parasite control practices included: the perceived expectation of others (i.e. Social norms) for implementing a quarantine strategy, farmer's suspicions to the presence of AR on the holding for instigating AR testing and the confirmation of AR for adopting FEC monitoring. Determining the influences of behaviour-specific factors on farmers' decision making processes will help to identify and address positive and negative influences concerning implementation of AR mitigating practices, as well as contribute to the development of more evidence based intervention strategies in the future.

Incidence and Outcomes of Nontraumatic Shock in Adults Using Emergency Medical Services in Victoria, Australia.

Importance: Nontraumatic shock is a challenging clinical condition, presenting urgent and unique demands in the prehospital setting. There is a paucity of data assessing its incidence, etiology, and clinical outcomes. Objective: To assess the incidence, etiology, and clinical outcomes of patients treated by emergency medical services (EMS) with nontraumatic shock using a large population-based sample. Design, Setting, and Participants: This population-based cohort study included consecutive adult patients with shock not related to trauma who received care by EMS between January 1, 2015, and June 30, 2019, in Victoria, Australia. Data were obtained from individually linked ambulance, hospital, and state death index data sets. During the study period there were 2 485 311 cases attended by EMS, of which 16 827 met the study's inclusion criteria for shock. Main Outcomes and Measures: The primary outcome was 30-day mortality. Secondary outcomes included length of hospital stay, emergency department discharge disposition, rates of coronary angiography and revascularization procedures, and the use of mechanical circulatory support. Results: A total of 12 695 patients were successfully linked, with a mean (SD) age of 65.7 (19.1) years; 6411 (50.5%) were men. The overall population-wide incidence of EMS-treated prehospital shock was 76 (95% CI, 75-77) per 100 000 person-years. An increased incidence was observed in men (79 [77-81] per 100 000 person-years), older patients (eg, aged 70-79 years: 177 [171-183] per 100 000 person-years), regional locations (outer regional or remote: 100 [94-107] per 100 000 person-years), and in areas with increased socioeconomic disadvantage (lowest socioeconomic status quintile: 92 [89-95] per 100 000 person-years). Patients with hospital outcome data were stratified into shock etiologies; 3615 (28.5%) had cardiogenic shock: 3998 (31.5%), septic shock; 1457 (11.5%), hypovolemic shock; and 3625 (28.6%), other causes of shock. Nearly one-third of patients (4158 [32.8%]) were deceased at 30 days. In multivariable analyses, increased age (all etiologies: hazard ratio [HR], 1.04; 95% CI, 1.03-1.04), female sex (cardiogenic shock: HR, 1.26; 95% CI, 1.12-1.42), increased initial heart rate (all etiologies: 1.01; 95% CI, 1.00-1.01), prehospital intubation (all etiologies: HR, 3.93; 95% CI, 3.48-4.44), and preexisting comorbidities (eg, chronic kidney disease, all etiologies: HR, 1.25; 95% CI, 1.10-1.42) were independently associated with 30-day mortality, while higher socioeconomic status (all etiologies: HR, 0.96; 95% CI, 0.94-0.98) and increased initial systolic blood pressure (all etiologies: HR, 0.99; 95% CI, 0.99-0.99) were associated with lower risk. Conclusions and Relevance: This population-level cohort study found that EMS-treated nontraumatic shock was a common condition, with a high risk of morbidity and mortality regardless of etiology. It disproportionately affected men, older patients, patients in regional areas, and those with social disadvantage. Further studies are required to assess how current systems of care can be optimized to improve outcomes.

An open-label, non-inferiority randomized controlled trial of lidocAine Versus Opioids In MyocarDial Infarction study (AVOID-2 study) methods paper.

Background There is increasing evidence that opioids interfere with the oral bioavailability of P2Y12 inhibitors leading to delayed onset of antiplatelet effects. Several strategies have been proposed to mitigate this interaction including utilizing alternative analgesic agents in the management of ischemic chest pain. Methods The lidocAine Versus Opioids In MyocarDial Infarction (AVOID-2) study is a phase II, pre-hospital, open-label, non-inferiority, randomized controlled trial conducted by Ambulance Victoria and Monash University in metropolitan Melbourne, Victoria, Australia. The purpose of the study is to compare the analgesic effect (reduction in pain by arrival to hospital) and safety (e.g. adverse drug reactions) (co-primary endpoints) of intravenous lidocaine versus intravenous fentanyl in 300 adult patients attended by ambulance with suspected ST-elevation myocardial infarction (STEMI). Secondary endpoints and a cardiac magnetic resonance imaging (MRI) sub-study will also compare infarct size between these two groups. Conclusions The evaluation of alternative analgesic agents in the management of acute coronary syndromes is urgently needed to manage the opioid-P2Y12 inhibitor interaction. The results of this trial will have significant implications on the emergency management of acute coronary syndromes internationally.

Currently Available Recombinant Alternatives to Horseshoe Crab Blood Lysates: Are They Comparable for the Detection of Environmental Bacterial Endotoxins? A Review.

Endotoxin testing by recombinant factor C (rFC) is increasing with the addition of new suppliers of reagents. By use of a recombinantly produced factor C , based on the sequence of a coagulation enzyme present in horseshoe crab amebocyte lysates, the rFC tests are designed as substitutes for the traditional Limulus amebocyte lysate (LAL)/Tachypleus amebocyte lysate tests based on horseshoe crab blood. Comparative testing of samples with both the LAL and recombinant reagents has shown a high degree of correlation, suggesting that use of rFC is comparable to the more traditional LAL tests and may be technologically superior. Recombinant factor C does not recognize the factor G pathway, the alternate coagulation pathway that the lysate reagents detect. This feature allows rFC to detect endotoxin more selectively. As a recombinantly produced material, it avoids the use of the horseshoe crabs required for lysate production, thereby protecting this species, which is at risk in some parts of the world. Recombinant factor C is expected to further benefit from a more sustainable supply chain based upon a robust biotechnological production process. We summarize here the results of many studies that evaluated the use of recombinant technology for the detection of environmental endotoxin. Additionally, we include a review of the current compendia and regulatory status of the recombinant technologies for use in the quality control of pharmaceutical manufacturing. Our analysis confirms that the recombinant technologies are comparable in protecting patient safety.

An international consensus on device-related pressure ulcers: SECURE prevention.

Catherine Milne and colleagues present the findings of their review, ccna2@juno.com.

A Novel Point-of-Care Solution to Streamline Local Wound Formulary Development and Promote Cost-effective Wound Care.

OBJECTIVE: To develop and implement a point-of-care digital solution to streamline the creation and maintenance of wound care product formularies and promote cost-effective wound management. METHODS: Researchers used Design Thinking methodology to develop the Formulary Module, a point-of-care digital solution within a clinical and reimbursement decision support web application for wound care and hyperbaric clinicians. The module was implemented in a US hospital-based outpatient wound clinic as follows: A baseline list of products was established, with brands automatically grouped by product category. Brands within each dressing category were compared, and redundancy eliminated. Study authors assessed the financial impact of formulary implementation in the wound clinic by comparing inventory expenditure before and after implementation. RESULTS: Implementation of the digital Formulary Module resulted in a 36% decrease in products (67 to 43 across 22 types), 38.73% decrease in the monthly average dollar spent on chargeable products, 29.56% decrease in the average dollar amount spent on chargeable products per patient visit, and increased staff efficiency. CONCLUSIONS: The Formulary Module has the potential to increase the adoption of cost-effective practices in wound care significantly.

Implementing Cognitive Science and Discipline-Based Education Research in the Undergraduate Science Classroom.

Cognitive science research on learning and instruction is often not directly connected to discipline-based research. In an effort to narrow this gap, this essay integrates research from both fields on five learning and instruction strategies: active retrieval, distributed (spaced) learning, dual coding, concrete examples, and feedback and assessment. These strategies can significantly enhance the effectiveness of science instruction, but they typically do not find their way into the undergraduate classroom. The implementation of these strategies is illustrated through an undergraduate science course for nonmajors called Science in Our Lives. This course provides students with opportunities to use scientific information to solve real-world problems and view science as part of everyday life.