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Abstract In the context of social events reopening and economic relaunch, sanitary surveillance of SARS-CoV-2 infection is still required. Here, we evaluated the diagnostic performances of a rapid, extraction-free and connected reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay on saliva. Nasopharyngeal (NP) swabs and saliva from 443 outpatients were collected simultaneously and tested by reverse-transcription quantitative PCR (RT-qPCR) as reference standard test. Seventy-one individuals (16.0%) were positive by NP and/or salivary RT-qPCR. Sensitivity and specificity of salivary RT-LAMP were 85.9% (95%CI 77.8–94.0%) and 99.5% (98.7–100%), respectively. Performances were similar for symptomatic and asymptomatic participants. Moreover, SARS-CoV-2 genetic variants were analyzed and no dominant mutation in RT-LAMP primer region was observed during the period of the study. We demonstrated that this RT-LAMP test on self-collected saliva is reliable for SARS-CoV-2 detection. This simple connected test with optional automatic results transfer to health authorities is unique and opens the way to secure professional and social events in actual context of economics restart.

As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.

The recently dominant SARS-CoV-2 Omicron JN.1 has evolved into multiple sublineages, with recurrent spike mutations R346T, F456L, and T572I, some of which exhibit growth advantages, such as KP.2 and KP.3. We investigated these mutations in JN.1, examining their individual and combined effects on immune evasion, ACE2 receptor affinity, and in vitro infectivity. F456L increased resistance to neutralization by human sera, including those after JN.1 breakthrough infections, and by RBD class-1 monoclonal antibodies, significantly altering JN.1 antigenicity. R346T enhanced ACE2-binding affinity and modestly boosted the infectivity of JN.1 pseudovirus, without a discernible effect on serum neutralization, while T572I slightly bolstered evasion of SD1-directed mAbs against JN.1's ancestor, BA.2, possibly by altering SD1 conformation. Importantly, expanding sublineages such as KP.2 containing R346T, F456L, and V1104L, showed similar neutralization resistance as JN.1 with R346T and F456L, suggesting V1104L does not appreciably affect antibody evasion. Furthermore, the hallmark mutation Q493E in KP.3 significantly reduced ACE2-binding affinity and viral infectivity, without noticeably impacting serum neutralization. Our findings illustrate how certain JN.1 mutations confer growth advantages in the population and could inform the design of the next COVID-19 vaccine booster.

IntroductionPrenatal exome sequencing (pES) can enhance genetic diagnosis of fetuses with structural anomalies and has recently been introduced as a national service in England. We aimed to examine service outcomes such as diagnostic yield (definite final diagnosis), referral rate, and sources of referral, and explore variation in outcomes of pES by individual or service level factors between 01 October 2021 and 30 June 2022.MethodspES testing results from the National Health Service laboratories performing testing were linked to National Congenital Anomaly and Rare Disease Registration Service data and the Maternity Services Data Set and descriptive statistics computed.ResultsThere were 475,089 women who gave birth in England during the study period. The referral rate for pES was 8.6 (95% CI 7.8, 9.4) per 10,000 maternities. About 59% of those referred proceeded with pES testing and 35% of women who proceeded received a definite final diagnosis with a median turnaround time of 15 days. Of those who had pES testing, 64.6% had a live birth, 25.3% underwent termination of pregnancy (median gestational age at termination: 26 weeks), and 9.3% had a stillbirth. Among the 85 women who had a definite final diagnosis, 40% had a termination of pregnancy, 18% had a stillbirth, and 42% had a live birth. The corresponding figures among women without a definite final diagnosis were 18%, 5%, and 78%, respectively. Among women who had a termination of pregnancy, the median gestational age at final report was 24.9 weeks and 26.2 weeks at termination. Variation observed in some of the characteristics and outcomes between regional services were limited by small sample size.ConclusionThis study showed that of those referred, pES testing provided a diagnosis for one in three pregnancies with a fetal anomaly across England during the study period when other tests had been non-informative. Women who opted for a termination of pregnancy underwent the procedure at relatively late gestations. Earlier referral for pES, streamlining pathways, and faster turnaround times may help results to be available at an earlier gestation to allow families more time to make decisions around continuing or terminating their pregnancy. The variation in service outcomes between regional services needs to be investigated further to understand the reasons for these differences.

Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies are substantially expanded 1 month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remains unknown. Here, we address this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from participants obtained at ∼1 month, ∼3 months, and ∼6 months post an XBB.1.5 MV booster. Our findings indicate that the resulting neutralizing antibody titers are robust and generally remain at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing that the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster.

IntroductionIn October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS.MethodsA survey (n = 159) and semi-structured interviews (n = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future.ResultsOverall, professionals were positive about the pES service with 77% rating it as Good or Excellent. A number of benefits were reported, including the increased opportunity for receiving actionable results for parental decision-making, improving equity of access to genomic tests and fostering close relationships between FM and genetics departments. Nonetheless, there was evidence that the shift to offering pES in a clinical setting had brought some challenges, such as additional clinic time, administrative processes, perceived lack of autonomy in decision-making regarding pES eligibility and difficulty engaging with peripheral maternity units. Concerns were also raised about the lack of confidence and gaps in genomics knowledge amongst non-genetics professionals - especially midwives. However, the findings also highlighted value in both FM, obstetric and genetics professionals benefiting from further training with a focus on recognising and managing prenatally diagnosed genetic conditions.ConclusionHealthcare professionals are enthusiastic about the benefits of pES, and through multi-collaborative working, have developed relationships that have contributed to effective communication across specialisms. Although limitations on resources and variation in knowledge about pES have impacted service delivery, professionals were hopeful that improvements to infrastructure and the upskilling of all professionals involved in the pathway would optimise the benefits of pES for both parents and professionals.

There is an urgent need for increased understanding of COVID-19 and strategies for its prevention, treatment, and mitigation. All participants in the research enterprise, including institutional review boards, have an ethical duty to protect participants and ensure that the benefits gained from such research do not conflict with the core principles that guided researchers prior to the pandemic. In this review, we discuss the ethical issues surrounding initiation and conduct of clinical trials, focusing on novel COVID-19 therapeutic, vaccine, or biospecimen research, using the principles of autonomy, beneficence, and justice. We discuss strategies to manage the practical challenges associated with the conduct of clinical trials, with an emphasis on maintaining the rights and welfare of research participants.

Introduction: Prenatal exome sequencing (pES) can enhance genetic diagnosis of fetuses with structural anomalies and has recently been introduced as a national service in England. We aimed to examine service outcomes such as diagnostic yield (definite final diagnosis), referral rate, and sources of referral, and explore variation in outcomes of pES by individual or service level factors between 01 October 2021 and 30 June 2022. Methods: pES testing results from the National Health Service laboratories performing testing were linked to National Congenital Anomaly and Rare Disease Registration Service data and the Maternity Services Data Set and descriptive statistics computed. Results: There were 475,089 women who gave birth in England during the study period. The referral rate for pES was 8.6 (95% CI 7.8, 9.4) per 10,000 maternities. About 59% of those referred proceeded with pES testing and 35% of women who proceeded received a definite final diagnosis with a median turnaround time of 15 days. Of those who had pES testing, 64.6% had a live birth, 25.3% underwent termination of pregnancy (median gestational age at termination: 26 weeks), and 9.3% had a stillbirth. Among the 85 women who had a definite final diagnosis, 40% had a termination of pregnancy, 18% had a stillbirth, and 42% had a live birth. The corresponding figures among women without a definite final diagnosis were 18%, 5%, and 78%, respectively. Among women who had a termination of pregnancy, the median gestational age at final report was 24.9 weeks and 26.2 weeks at termination. Variation observed in some of the characteristics and outcomes between regional services were limited by small sample size. Conclusion: This study showed that of those referred, pES testing provided a diagnosis for one in three pregnancies with a fetal anomaly across England during the study period when other tests had been non-informative. Women who opted for a termination of pregnancy underwent the procedure at relatively late gestations. Earlier referral for pES, streamlining pathways, and faster turnaround times may help results to be available at an earlier gestation to allow families more time to make decisions around continuing or terminating their pregnancy. The variation in service outcomes between regional services needs to be investigated further to understand the reasons for these differences. [ABSTRACT FROM AUTHOR]

Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June–August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers. In both states, a convenience sample of persons who work in dairies was interviewed, and blood specimens were collected. Among 115 persons, eight (7%; 95% CI = 3.6%–13.1%) had serologic evidence of recent infection with A(H5) virus; all reported milking cows or cleaning the milking parlor. Among persons with serologic evidence of infection, four recalled being ill around the time cows were ill; symptoms began before or within a few days of A(H5) virus detections among cows. This finding supports the need to identify and implement strategies to prevent transmission among dairy cattle to reduce worker exposures and for education and outreach to dairy workers concerning prevention, symptoms, and where to seek medical care if the workers develop symptoms. Timely identification of infected herds can support rapid initiation of monitoring, testing, and treatment for human illness, including mild illness, among exposed dairy workers. [ABSTRACT FROM AUTHOR]

The risk for transmission of highly pathogenic avian influenza A(H5N1) virus from dairy cows to humans is currently low; however, personal protective equipment (PPE) use during work activities on dairy farms has not been well described. PPE use can protect farmworkers when they are working with highly pathogenic avian influenza A(H5N1)–infected cows. The Colorado Department of Public Health and Environment (CDPHE) and the Colorado Department of Agriculture (CDA) offered PPE to all Colorado farms before or during an A(H5N1) outbreak in cows in 2024. CDPHE surveyed 83 dairy workers from three farms with a confirmed bovine A(H5N1) outbreak. Frequently reported farm worker activities included milking cows or working in the milking parlor (51%), cleaning cow manure (49%), and transporting cows (46%). Frequently reported PPE items available to workers before A(H5N1) outbreaks included gloves (88%), eye protection (e.g., safety glasses or goggles) (76%), rubber boots or boot covers (71%), and head covers (69%). N95 respirator use was low among workers who were exposed to ill cows after detection of A(H5N1) virus (26%). PPE use while working with ill cows increased a mean of 28% after detection of A(H5N1) virus on surveyed farms; use of eye protection while milking cows increased the most (40%). Public health PPE distribution, education, and collaboration with CDA might have increased PPE use on dairy farms with A(H5N1) virus–infected cows and mitigated risk for farmworkers acquiring A(H5N1) virus. [ABSTRACT FROM AUTHOR]

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder, characterized by progressive heterotopic ossification (HO) and painful soft-tissue inflammatory flare-ups. This was a post hoc analysis from a phase 2 (NCT03188666) trial in which adults with FOP received intravenous anti-activin A antibody garetosmab 10 mg/kg or placebo every 4 wk over 28 wk (Period 1), followed by a 28-wk open-label treatment and extension (Periods 2 and 3). Here we describe flare-ups, their relationship to new HO lesions, and the impact of garetosmab on flare-ups. Volume of new HO lesions was measured by CT. Patient-reported flare-ups were defined by any 2 of the following: new onset of pain, swelling, joint stiffness, decrease in movement, or perceived presence of HO. Flare-ups were experienced by 71% (17/24) of placebo-treated patients, 59% (10/17) of whom developed a new HO lesion irrespective of flare-up location; 24% of flare-ups location-matched new HO lesions. Twenty-nine new HO lesions occurred in the placebo cohort by week 28, of which 12 (41%) occurred in the same location as new or ongoing flare-ups. A higher volume of newly formed heterotopic bone (week 28) occurred in placebo-treated patients who had experienced a prior flare-up vs those without (median [Q1:Q3] of 16.6 [12.0:31.1] vs 3.2 cm3). Garetosmab was previously shown to decrease patient-reported flare-up frequency in Period 1; here, garetosmab reduced the median (Q1:Q3) duration of patient-reported flares (15.0 [6.0:82.0] vs 48.0 [15.0:1.00] d) and the severity of flare-ups vs placebo. Frequency of corticosteroid use was numerically reduced in those treated with garetosmab (40.0%) vs placebo (58.3%). In this analysis, 71% of placebo-treated adults with FOP experienced flare-ups over 28 wk, which were associated with an increased volume of newly formed heterotopic bone. Garetosmab reduced the severity and duration of flare-ups, with effects sustained during the entire trial. Lay Summary: Fibrodysplasia ossificans progressiva (FOP) is a very rare genetic disorder caused by mutations in the ACVR1 gene. People with FOP experience growth of new bone in places where bone does not usually develop. Soft tissues (like skeletal muscles) and connective tissues (like tendons and ligaments) are gradually replaced by bone beyond the normal skeleton—a process called heterotopic ossification (HO). People with FOP experience flare-ups, which are painful swellings of the soft tissues. In this clinical study in people with FOP, we looked at the number of flareups, whether flareups were linked to new HO lesions, and the impact of garetosmab (a monoclonal antibody) on flareups. At random, about half the patients received placebo, or inactive drug, with the other half receiving garetosmab, the study drug. Of the patients who received placebo, 71% had flare-ups and 59% percent of those who had flare-ups also had a new HO lesion, which was not always related to the location of the flare-up. We have previously shown that garetosmab reduces the number of flareups patients report. In this study, we show that garetosmab reduces the length and pain severity of flare-ups too. The treatment effects were maintained for the whole study. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic was an unparalleled stressor that enhanced isolation. Loneliness has been identified as an epidemic by the US Surgeon General. This study aimed to: (1) characterize longitudinal trajectories of loneliness during the acute phase of the COVID‐19 pandemic; (2) identify longitudinal mediators of the relationship of loneliness with anxiety and depression; and (3) examine how loneliness naturally clusters and identify factors associated with high loneliness. Two hundred and twenty‐nine adults (78% female; mean age = 39.5 ± 13.8) completed an abbreviated version of the UCLA Loneliness Scale, Perceived Stress Scale, Emotion Regulation Questionnaire, State Anxiety Inventory, and Patient Health Questionnaire‐8 longitudinally between April 2020 and 2021. Trajectory analyses demonstrated relatively stable loneliness over time, while anxiety and depression symptoms declined. Longitudinal analyses indicated that loneliness effects on anxiety and depression were both partially mediated by perceived stress, while emotion regulation capacity only mediated effects on anxiety. Three stable clusters of loneliness trajectories emerged (high, moderate, and low). The odds of moderate or high loneliness cluster membership were positively associated with higher perceived stress and negatively associated with greater cognitive reappraisal use. Our results demonstrate the important interconnections between loneliness and facets of mental health throughout the early phases of the pandemic and may inform targeted future interventions for loneliness work. [ABSTRACT FROM AUTHOR]

Background: Prenatal exome sequencing (ES) for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the NHS Genomic Medicine Service (GMS). The GMS is based around seven regional Genomic Laboratory Hubs (GLHs). Prenatal ES has the potential to significantly improve NHS prenatal diagnostic services by increasing genetic diagnoses and informing prenatal decision-making. Prenatal ES has not previously been offered routinely in a national healthcare system and there are gaps in knowledge and guidance. Methods: Our mixed-methods evaluation commenced in October 2020, aligning with the start date of the NHS prenatal ES service. Study design draws on a framework developed in previous studies of major system innovation. There are five interrelated workstreams. Workstream-1 will use interviews and surveys with professionals, non-participant observations and documentary analysis to produce in-depth case studies across all GLHs. Data collection at multiple time points will track changes over time. In Workstream-2 qualitative interviews with parents offered prenatal ES will explore experiences and establish information and support needs. Workstream-3 will analyse data from all prenatal ES tests for nine-months to establish service outcomes (e.g. diagnostic yield, referral rates, referral sources). Comparisons between GLHs will identify factors (individual or service-related) associated with any variation in outcomes. Workstream-4 will identify and analyse practical ethical problems. Requirements for an effective ethics framework for an optimal and equitable service will be determined. Workstream-5 will assess costs and cost-effectiveness of prenatal ES versus standard tests and evaluate costs of implementing an optimal prenatal ES care pathway. Integration of findings will determine key features of an optimal care pathway from a service delivery, parent and professional perspective. Discussion: The proposed formative and summative evaluation will inform the evolving prenatal ES service to ensure equity of access, high standards of care and benefits for parents across England.

Abstract A structured approach is critical to the success of any small group teaching session; preparation and planning are key elements in ensuring the session is systematic and effective. Learning activities guide and engage students towards the achievement of agreed learning outcomes. This paper introduces the central concepts of planning and preparing a small group teaching session. It provides an overview of key theoretical principles in lesson planning, delivery, and how to provide effective feedback in this setting.

Abstract Team-based learning (TBL) provides an active, structured form of small group learning, that can be applied to large classes. Student accountability is achieved through the specific steps of TBL, including pre-class preparation, readiness assurance testing, problem-solving activities, and immediate feedback. Globally, a growing number of healthcare faculties have adopted TBL in a variety of combinations, across diverse settings and content areas. This paper provides a succinct overview of TBL and guidance for teachers towards successful design and implementation of TBL within health professional education. It also offers guidance for students participating in TBL. The paper is informed by both educational theory, and the extensive, seven year experience of the first and last authors in designing, implementing, facilitating and evaluating TBL at a large medical school.

Abstract The teaching of procedural skills required for clinical practice remains an ongoing challenge in healthcare education. Health professionals must be competent to perform a wide range of clinical skills, and are also regularly required to teach these clinical skills to their peers, junior staff, and students. Teaching of procedural skills through the use of frameworks, observation and provision of feedback, with opportunities for repeated practice assists in the learners’ acquisition and retention of skills. With a focus on the teaching of non-complex skills, this paper explores how skills are learned; ways to improve skill performance; determining competency; and the provision of effective feedback.

Abstract Provision of feedback forms an integral part of the learning process. Receipt of feedback enriches the learning experience, and helps to narrow the gap between actual and desired performance. Effective feedback helps to reinforce good practice, motivating the learner towards the desired outcome. However, a common complaint from learners is that the receipt of feedback is infrequent and inadequate. This paper briefly explores the role of feedback within the learning process, the barriers to the feedback process, and practical guidelines for facilitating feedback.

Abstract Interprofessional education (IPE) is a critical approach for preparing students to enter the health workforce, where teamwork and collaboration are important competencies. IPE has been promoted by a number of international health organisations, as part of a redesign of healthcare systems to promote interprofessional teamwork, to enhance the quality of patient care, and improve health outcomes. In response, universities are beginning to create and sustain authentic and inclusive IPE activities, with which students can engage. A growing number of health professionals are expected to support and facilitate interprofessional student groups. Designing interprofessional learning activities, and facilitating interprofessional groups of students requires an additional layer of skills compared with uniprofessional student groups. This article outlines the key points for planning and practicing interprofessional facilitation within the classroom and clinical setting.

Susan McKenzie,1 Annette Burgess,2 Craig Mellis1 1Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; 2Education Office, Sydney Medical School, The University of Sydney, Sydney, NSW, AustraliaCorrespondence: Susan McKenzieCentral Clinical School, Sydney Medical School, The University of Sydney, Building 63, Level 4, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW 2050, AustraliaTel +61 2 9515 6548Email susan.mckenzie@sydney.edu.auIntroduction: Medical students extend their preparatory learning on entering the clinical work environment, by joining their clinical team as peripheral participants and start to care for “real” patients. This learning is situated, experiential, varied, mainly unstructured, highly dependent on clinical opportunities (affordances), and students’ motivation to learn (learner agency). Students ideally contribute to workplace activities, which allow their practical skills, confidence and professional identity to evolve. This study sought to investigate senior students’ perspectives in their early stages of workplace learning, by using social learning theory as a framework. The focus is on team integration, practical skills performance, professional development and their evolving professional identity.Methods: Between 2015 and 2018, we conducted five focus groups, with a total of 36 volunteers, out of a possible 200 (18% Stage 3 (Year 3)) medical students. Each focus group session was audio recorded and transcribed verbatim. Participants were de-identified, and framework analysis used the theoretical frameworks of communities of practice, and workplace affordances to gain insight into their work-place learning experience during the first two months of their clinical rotation.Results: Thirty-six students out of 200 (18%) attended focus groups over a four-year period. The results are presented using the theoretical frameworks of community of practice and workplace affordances and presented as themes of: meaning, “learning as experience”, practice, “learning as doing” community, “learning as belonging”, and identity, “learning as becoming”.Discussion: Participants reported many positive examples of workplace learning while dealing directly with patients. Students were also exposed to ethical dilemmas and unexpected risks in the workplace. These included lack of site orientation, unsupportive teams, lack of supervision, and students’ inability to initiate agency, all of which contributed to their workplace uncertainty. Performing manageable tasks for their team provided a role in their community of practice, strengthening their identity as evolving doctors. Exposure to both positive and negative role models allowed students to reflect on ethical issues, further extending their own professional identities.Summary: Participants were quick to observe and report workplace dynamics as they were exposed to the positive and negative aspects of the hidden curriculum. This allowed them to reflect on patient safety, and ethical concerns promoting the development of their professional identity.Keywords: third-year medicine, workplace learning, professional identity, role modelling, communities of practice