Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine.

BACKGROUND: Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population. METHODS: In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-µg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline. RESULTS: A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. CONCLUSIONS: A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16.).

The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial.

BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. METHODS: Adults aged 18-84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. RESULTS: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%-88.8%). Vaccine efficacy was 100% (95% CI, 17.9%-100.0%) against severe disease and 76.3% (95% CI, 57.4%-86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. CONCLUSIONS: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. CLINICAL TRIALS REGISTRATION: EudraCT, 2020-004123-16.

Impact of occupational stress on healthcare workers' family members before and during COVID-19: A systematic review.

We aimed to explore the experiences, needs, and mental health impact of family members of healthcare workers (HCWs) before and during the COVID-19 pandemic. Eleven quantitative and nine qualitative studies were included in this review. Based on the narrative synthesis, we identified five outcomes: 'Mental health outcomes', 'Family relationships, 'Coping skills and resilience', 'Quality of life and social life', and 'Practical outcomes'. Our findings indicated that there was a high risk to the mental health and well-being of families of healthcare workers both before and during the pandemic. However, with the COVID-19 pandemic, some experiences and mental health issues of families were worsened. There was also a negative association between working long hours/shift work and family relationships/communication, family social life, and joint activities, and family members taking on more domestic responsibilities. Families tended to use both positive and negative coping strategies to deal with their loved one's job stress. Organisations and support services working with people in health care work should consider widening support to families where possible. With this understanding, HCWs and their families could be supported more effectively in clinical and organisational settings. Trial registration: Systematic Review Registration Number: CRD42022310729. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022310729.

'Helper' or 'punisher'? A qualitative study exploring staff experiences of treating severe and complex eating disorder presentations in inpatient settings.

BACKGROUND: Eating disorders have been described as challenging to treat, with the most severe cases requiring inpatient admission. Previous studies have explored staff's perspectives on eating disorders and service provision. However, little is currently known about how staff experience working with severe and complex eating disorder presentations in inpatient settings and how they may be impacted by their work. AIMS: This study aimed to explore the experiences of staff who contribute towards the treatment of severe and complex eating disorder presentations in inpatient settings. METHODS: Participants were recruited purposively via clinical contacts and a private hospital group in the UK. Semi-structured interviews were conducted, recorded, transcribed verbatim, and analysed guided by the principles of reflexive thematic analysis. RESULTS: Interviews were completed with twelve staff members, including frontline nursing staff and multidisciplinary team (MDT) staff, from both private and public specialist settings. Participants expressed uncertainty about the treatment approach for service-users with severe and complex presentations. As service-users often resisted treatment, participants felt positioned as a 'punisher' rather than a 'helper' in initial treatment stages. Many had experienced physically and emotionally impactful events at work, including violence and aggression, as well as serious incidents of self-harm and suicide attempts. Participants generally found support in their colleagues, however considered organisational support insufficient. CONCLUSIONS: This research highlights an urgent need to consider the wellbeing of staff who works in eating disorder inpatient settings, as well as their support needs. Retention and recruitment strategies should be reviewed to reduce staff turnover and improve patient care. Further research should investigate whether specialist inpatient staff are impacted by symptoms of vicarious or direct trauma, moral injury and compassion fatigue.

This study explored how staff who treat severe and complex eating disorders experience working in inpatient settings. The researchers interviewed twelve staff members from inpatient eating disorder services based throughout the UK. The themes identified from the interview data described challenges related to treating people under the Mental Health Act (without their consent) and the dynamics that arise in this context ­ staff often found it hard to be seen as 'the punisher' when delivering treatment, as it felt like a contradiction to their career in helping others. Staff described physically and emotionally taxing work and their reliance on co-workers in coping with this, as they found organisational support insufficient. Several staff described experiencing directly and indirectly (vicariously) traumatising events at work. This highlights an urgent need to investigate trauma responses in the context of inpatient work with severe and complex eating disorders, as this will enable organisations to implement appropriate staff support. This is likely to in turn improve patient care.

"Fix the system the people who are in it are not the ones that are broken" A qualitative study exploring UK academic researchers' views on support at work.

Recent evidence suggests that it remains difficult for academic researchers to preserve global well-being when working in the UK higher education sector. Our study aimed to explore academic researchers' perspectives on how they feel their mental health and well-being could be better supported within the UK higher education system. Using a combination of semi-structured and narrative interviewing techniques, we gathered the perspectives of 26 researchers. Narrative and reflexive thematic analysis were then used on the data collected. Our findings highlight the need to tackle systemic issues such job insecurity and unrealistically high workloads, given the risk they can pose to researchers' mental health and well-being. Our findings also highlight the key influence of managers and supervisors in creating a supportive environment, and the importance of going beyond what support is offered. That is, it is vital to effectively promote any existing or emerging support systems, and to be proactive in offering this support. Given the diversity identified in researchers' individual situations, it is important that support is flexible and takes into consideration individual requirements and preferences. Higher education authorities and institutions need to determine how they can foster a healthy, caring environment for researchers working in this sector going forwards.

Expert international trauma clinicians' views on the definition, composition and delivery of reintegration interventions for complex PTSD.

Background: Research has previously distinguished between complex post-traumatic stress disorder (CPTSD) and PTSD, with the former including a range of disturbances in self-regulatory capacities in addition to difficulties associated with PTSD. Clinical guidelines have previously recommended a phase-based approach for the treatment of CPTSD, yet the final 'reintegration' phase of treatment has been overlooked in research, with limited evidence into its value and effectiveness, and inconsistencies in its definitions and understanding.Objective: We set out to define and determine the key principles of 'reintegration' and to specify the components and method of delivery of treatment.Method: Leading national and international clinical and academic experts in CPTSD were interviewed and asked about their views of how 'reintegration' should be defined, its role in the treatment of CPTSD, what it should be composed of, the key principles of its delivery, and how it should be evaluated. We analysed transcripts of the interviews following the principles of Codebook Thematic Analysis.Results: We conducted 16 interviews with leading national and international experts with at least 10 years' experience of treating people with CPTSD. Themes derived from our analysis demonstrated that while the definition and composition of reintegration varied greatly between experts, the key principles in its delivery were consistent across all experts.Conclusions: The results of this study lay the foundation for a framework of what reintegration is and how it can be used in, but also highlight the need for more research to be conducted on the role of reintegration in the treatment of CPTSD. Consensus for the definition and composition of reintegration is still yet to be reached. Possible measures for evaluating reintegration should also be explored in the future.

Reintegration is one of the recommended phases of treatment for CPTSD, however recent research has found that there are inconsistencies in its definition, role and value.The current study shows the opinions of experts, highlighting areas of consensus as well as differences in views with regards to the definition, composition and key principles in the delivery of reintegration.

Post-incident psychosocial interventions after a traumatic incident in the workplace: a systematic review of current research evidence and clinical guidance.

Background: After a traumatic incident in the workplace organisations want to provide support for their employees to prevent PTSD. However, what is safe and effective to offer has not yet been established, despite many organisations offering some form of intervention after a traumatic event.Objective: To systematically review the evidence for post-incident psychosocial interventions offered within one month of a workplace trauma, and to compare the content, effectiveness and acceptability of these interventions. Given the lack of a yet clearly established evidence-base in this field, we sought to examine both published empirical research as well as guidelines published by expert groups working with staff in high-risk roles.Methods: We conducted systematic searches for empirical research across bibliographic databases and searched online for clinical practice guidelines to April 2023. We were also referred to potentially relevant literature by experts in workplace trauma. Both empirical research and clinical guidelines were appraised for their quality.Results: A total of 80 research studies and 11 clinical practice guidelines were included in the review. Interventions included Critical Incident Stress Debriefing (CISD), Critical Incident Stress Management (CISM), unspecified Debriefing, Trauma Risk Management (TRiM), Psychological First Aid (PFA), EMDR, CBT and group counselling. Most research and guidance were of poor quality. The findings of this review do not demonstrate any harm caused by CISD, CISM, PFA, TRiM, EMDR, group counselling or CBT interventions when delivered in a workplace setting. However, they do not conclusively demonstrate benefits of these interventions nor do they establish superiority of any specific intervention. Generic debriefing was associated with some negative outcomes. Current clinical guidelines were inconsistent with the current research evidence base. Nevertheless, interventions were generally valued by workers.Conclusions: Better quality research and guidance is urgently needed, including more detailed exploration of the specific aspects of delivery of post-incident interventions.

Organisations often seek to provide some form of psychosocial intervention after a traumatic event in the workplace.Previous reviews have contraindicated particular forms of 'debriefing', however, the evidence for post-incident psychosocial interventions in the workplace has not previously been systematically reviewed.Research evidence was generally of poor quality with limited evidence of effectiveness and clinical guidelines were inconsistent with the evidence. Nevertheless, research did not demonstrate harm from most established interventions and support was valued by workers.

The impact of working in academia on researchers' mental health and well-being: A systematic review and qualitative meta-synthesis.

OBJECTIVE: To understand how researchers experience working in academia and the effects these experiences have on their mental health and well-being, through synthesizing published qualitative data. METHOD: A systematic review and qualitative meta-synthesis was conducted to gain a comprehensive overview of what is currently known about academic researchers' mental health and well-being. Relevant papers were identified through searching electronic databases, Google Scholar, and citation tracking. The quality of the included studies was assessed and the data was synthesised using reflexive thematic analysis. RESULTS: 26 papers were identified and included in this review. Academic researchers' experiences were captured under seven key themes. Job insecurity coupled with the high expectations set by the academic system left researchers at risk of poor mental health and well-being. Access to peer support networks, opportunities for career progression, and mentorship can help mitigate the stress associated with the academic job role, however, under-represented groups in academia are at risk of unequal access to resources, support, and opportunities. CONCLUSION: To improve researchers' well-being at work, scientific/academic practice and the system's concept of what a successful researcher should look like, needs to change. Further high-quality qualitative research is needed to better understand how systemic change, including tackling inequality and introducing better support systems, can be brought about more immediately and effectively. Further research is also needed to better understand the experiences and support needs of post-doctoral and more senior researchers, as there is a paucity of literature in this area. TRIAL REGISTRATION: The review protocol was registered on PROSPERO (CRD42021232480).

'Very hit and miss': an interpretive phenomenological analysis of ambulance service care for young people experiencing mental health crisis.

Introduction: The ambulance service provides vital front line mental healthcare for young people in crisis, but there is a lack of evidence to guide best practice in this area. The lived experiences of service users can offer important insights to guide service development, therefore we carried out a qualitative evaluation of care provided by the ambulance service to young people experiencing a mental health-related emergency. Methods: Ten participants aged 16-25 years who had used the ambulance service due to a mental health crisis within the past 2 years were interviewed about their experiences and view of the care they received. Interviews were transcribed verbatim and interpretative phenomenological analysis used to explore participants' individual narratives and identify recurrent themes. Results: A theme of inconsistent quality of care was evident in all participants' accounts. Contributing to this superordinate theme were six recurrent themes: positive qualities of individual ambulance clinicians, ambivalence about seeking care, the importance of retaining agency, need for mental health training for ambulance clinicians, need for inter-service collaboration and favourable comparison of the ambulance service to other services. Conclusions: We identified some examples of good practice, including person-centred care, respect for patient autonomy and attending to physical health needs. However, our findings suggest the quality of ambulance service mental healthcare is not yet sufficiently consistent. In the absence of mandatory high-quality mental health training and evidence-based protocols, the quality of care appears largely dependent on the qualities and experience of individual ambulance clinicians.

Acute otitis externa: Consensus definition, diagnostic criteria and core outcome set development.

OBJECTIVE: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE. STUDY DESIGN: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition. SETTING: Stakeholders from the United Kingdom. SUBJECTS AND METHODS: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition. RESULTS: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'. CONCLUSION: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life.