Lessons learned from the first 50 COVID-19 critical care transfer missions conducted by a civilian UK Helicopter Emergency Medical Service team.

BACKGROUND: The COVID-19 pandemic has placed exceptional demand on Intensive Care Units, necessitating the critical care transfer of patients on a regional and national scale. Performing these transfers required specialist expertise and involved moving patients over significant distances. Air Ambulance Kent Surrey Sussex created a designated critical care transfer team and was one of the first civilian air ambulances in the United Kingdom to move ventilated COVID-19 patients by air. We describe the practical set up of such a service and the key lessons learned from the first 50 transfers. METHODS: Retrospective review of air critical care transfer service set up and case review of first 50 transfers. RESULTS: We describe key elements of the critical care transfer service, including coordination and activation; case interrogation; workforce; training; equipment; aircraft modifications; human factors and clinical governance. A total of 50 missions are described between 18 December 2020 and 1 February 2021. 94% of the transfer missions were conducted by road. The mean age of these patients was 58 years (29-83). 30 (60%) were male and 20 (40%) were female. The mean total mission cycle (time of referral until the time team declared free at receiving hospital) was 264 min (range 149-440 min). The mean time spent at the referring hospital prior to leaving for the receiving unit was 72 min (31-158). The mean transfer transit time between referring and receiving units was 72 min (9-182). CONCLUSION: Critically ill COVID-19 patients have highly complex medical needs during transport. Critical care transfer of COVID-19-positive patients by civilian HEMS services, including air transfer, can be achieved safely with specific planning, protocols and precautions. Regional planning of COVID-19 critical care transfers is required to optimise the time available of critical care transfer teams.

Prolonged P wave duration is associated with right atrial dimensions, but not atrial arrhythmias, in middle-aged endurance athletes.

BACKGROUND: Atrial arrhythmias occur at a higher than expected prevalence amongst endurance athletes. Few studies have examined both atrial structure and arrhythmias in middle-aged endurance athletes. We examined the relationship between P-wave duration, atrial dimensions, and the presence of atrial ectopy in long-standing, middle-aged endurance athletes. METHODS: Middle-aged athletes with a minimum of 10 years of competitive endurance sport history and no history of structural heart disease or clinical atrial arrhythmias, had 12-lead ECGs to assess P-wave duration, signal-averaged ECGs (SAECG) to assess filtered P-wave duration, a 24 h Holter monitor to assess atrial ectopy, and echocardiography and cardiac magnetic resonance imaging to assess atrial structural characteristics. RESULTS: Amongst endurance athletes (n = 104; mean age = 54 ±â€¯5 years; 63% male), filtered P-wave duration on SAECG was correlated with P-wave duration on 12-lead ECG (r = 0.36, p, 0.0001), as well as with larger CMR-derived RA areas (r = 0.30, p = 0.01) and volumes (r = 0.24, p < 0.05). There was no correlation between filtered P-wave duration and any LA measures on imaging (p > 0.05). There was no correlation between the incidence of atrial ectopy (premature atrial contractions or atrial tachycardia) and any electrocardiographic or structural measures. CONCLUSION: Longer filtered P-wave duration was associated with larger RA areas and volumes, without an increase in atrial ectopy.

Meningococcal Disease in Northern Ireland - Past, Present & Future: MeningoNI Forum.

Meningococcal disease has had devastating consequences in Northern Ireland since its first description locally in 1859. The incidence of this disease has significantly declined in recent years, however it is important to understand reasons for this changing epidemiology and to acknowledge the diagnostic and clinical management developments that have been made locally. This review aims to examine the changing face of this disease in Northern Ireland over the years, with particular reference to local disease prevention, epidemiology, diagnosis, clinical treatment and management, post-disease sequelae and the role of meningitis charities locally, in terms of patient support and research.

Magnetic resonance imaging reveals elevated aortic pulse wave velocity in obese and overweight adolescents.

The aortic pulse wave velocity (PWV) measured via cardiac magnetic resonance (CMR) can be used to non-invasively assess changes in arterial stiffness and potential underlying vascular dysfunction. This technique could unmask early arterial dysfunction in overweight and obese youth at risk for cardiovascular disease. We sought to determine the association between vascular stiffness, percentage body fat, body mass index (BMI), and cardiac function in adolescents across the weight spectrum through both CMR and standard applanation tonometry (AT)-based PWV measurements. PWV and left-ventricular cardiac function were assessed using 3.0 T CMR in obese and overweight (OB/OW) participants (n = 12) and controls (n = 7). PWV was also estimated via carotid-femoral AT. OB/OW participants did not differ from healthy-weight controls regarding cardiometabolic risk factors or physical activity levels, but there was a trend towards higher levels of triglycerides in obese/overweight participants (P = 0.07). Mean PWV was higher in obese participants when corrected for age and sex (P = 0.01), and was positively associated with BMI (ß = 0.51, P = 0.02). PWV estimated through AT was not significantly different between groups. Cardiac function measured by left-ventricular ejection fraction z-score was inversely associated with mean PWV (ß = -0.57, P = 0.026). Increasing arterial stiffness and decreasing cardiac function were evident among our overweight and obese cohort. PWV estimated by CMR could detect early increases in arterial stiffness vs. traditional AT measurements of PWV.

A systematic review and thematic synthesis of patients' experience of medicines adherence.

BACKGROUND: Medicines non-adherence continues to be problematic in health care practice. After decades of research, few interventions have a robust evidence-based demonstrating their applicability to improve adherence. Phenomenology has a place within the health care research environment. OBJECTIVE: To explore patients' lived experiences of medicines adherence reported in the phenomenonologic literature. METHODS: A systematic literature search was conducted to identify peer-reviewed and published phenomenological investigations in adults that aimed to investigate patients' lived experiences of medicines adherence. Studies were appraised using the Critical Appraisal Skills Programme (CASP) Qualitative Research Tool. Thematic synthesis was conducted using a combination of manual coding and NVivo10 [QSR International, Melbourne] coding to aid data management. RESULTS: Descriptive themes identified included i) dislike for medicines, ii) survival, iii) perceived need, including a) symptoms and side-effects and b) cost, and iv) routine. Analytic themes identified were i) identity and ii) interaction. CONCLUSIONS: This work describes adherence as a social interaction between the identity of patients and medicines, mediated by interaction with family, friends, health care professionals, the media and the medicine, itself. Health care professionals and policy makers should seek to re-locate adherence as a social phenomenon, directing the development of interventions to exploit patient interaction with wider society, such that patients 'get to know' their medicines, and how they can be taken, throughout the life of the patient and the prescription.

E3 ligase EDD1/UBR5 is utilized by the HPV E6 oncogene to destabilize tumor suppressor TIP60.

Tat-interacting protein of 60 kDa (TIP60) is an essential lysine acetyltransferase implicated in transcription, DNA damage response and apoptosis. TIP60 protein expression is reduced in cancers. In cervical cancers, human papillomavirus (HPV) E6 oncogene targets cellular p53, Bak and some of the PDZ domain-containing proteins for proteasome-mediated degradation through E6AP ligase. Recently, E6 oncogene from high-risk and low-risk categories was also shown to target TIP60. However, the molecular mechanisms and whether destabilization of TIP60 contributes to HPV E6-mediated transformation remain unanswered. Our proteomic analyses revealed EDD1 (E3 identified by differential display), an E3 ligase generally overexpressed in cancers as a novel interacting partner of TIP60. By investigating protein turnover and ubiquitination assays, we show that EDD1 negatively regulates TIP60's stability through the proteasome pathway. Strikingly, HPV E6 uses this function of EDD1 to destabilize TIP60. Colony-formation assays and soft agar assays show that gain of function of TIP60 or depletion of EDD1 in HPV-positive cervical cancer cells significantly inhibits cell growth in vitro. This phenotype is strongly supported by the in-vivo studies where re-activation of TIP60 in cervical cancer cells dramatically reduces tumor formation. In summary, we have discovered a novel ligase through which E6 destabilizes TIP60. Currently, in the absence of an effective therapeutic vaccine for malignant cervical cancers, cervical cancer still remains to be a major disease burden. Hence, our studies implying a distinct tumor suppressor role for TIP60 in cervical cancers show that reactivation of TIP60 could be of therapeutic value.

Angelman syndrome-associated ubiquitin ligase UBE3A/E6AP mutants interfere with the proteolytic activity of the proteasome.

Angelman syndrome, a severe neurodevelopmental disease, occurs primarily due to genetic defects, which cause lack of expression or mutations in the wild-type E6AP/UBE3A protein. A proportion of the Angelman syndrome patients bear UBE3A point mutations, which do not interfere with the expression of the full-length protein, however, these individuals still develop physiological conditions of the disease. Interestingly, most of these mutations are catalytically defective, thereby indicating the importance of UBE3A enzymatic activity role in the Angelman syndrome pathology. In this study, we show that Angelman syndrome-associated mutants interact strongly with the proteasome via the S5a proteasomal subunit, resulting in an overall inhibitory effect on the proteolytic activity of the proteasome. Our results suggest that mutated catalytically inactive forms of UBE3A may cause defects in overall proteasome function, which could have an important role in the Angelman syndrome pathology.

Consultant and trainee attitudes towards supervision of operative procedures in the UK and Ireland.

The e-logbook is used to monitor progression through training and to assess training within teaching units. We document consultant and trainee opinions with regards to supervision status, and to inform guidelines for trainees and trainers using the e-logbook. A questionnaire was sent to consultants and trainees in the UK and Ireland. Eight theatre scenarios were described and respondents were asked to state what they felt was the appropriate supervision status for the trainee. Significantly more consultants in the UK use the e-logbook than those based in Ireland (58.5%:14.5%). There were differences in consensus response to the scenarios between consultants and trainees, and between Irish and UK based surgeons. We have documented the opinions of consultants and trainees from across the UK and Ireland with regards to supervision status for trainees under certain theatre situations. This information should support formal guidelines for all users of the logbook.

Dissection of the C-terminal region of E1A redefines the roles of CtBP and other cellular targets in oncogenic transformation.

Human adenovirus E1A makes extensive connections with the cellular protein interaction network. By doing so, E1A can manipulate many cellular programs, including cell cycle progression. Through these reprogramming events, E1A functions as a growth-promoting oncogene and has been used extensively to investigate mechanisms contributing to oncogenesis. Nevertheless, it remains unclear how the C-terminal region of E1A contributes to oncogenic transformation. Although this region is required for transformation in cooperation with E1B, it paradoxically suppresses transformation in cooperation with activated Ras. Previous analysis has suggested that the interaction of E1A with CtBP plays a pivotal role in both activities. However, some C-terminal mutants of E1A retain CtBP binding and yet exhibit defects in transformation, suggesting that other targets of this region are also necessary. To explore the roles of these additional factors, we performed an extensive mutational analysis of the C terminus of E1A. We identified key residues that are specifically required for binding all known targets of the C terminus of E1A. We further tested each mutant for the ability to both localize to the nucleus and transform primary rat cells in cooperation with E1B-55K or Ras. Interaction of E1A with importin α3/Qip1, dual-specificity tyrosine-regulated kinase 1A (DYRK1A), HAN11, and CtBP influenced transformation with E1B-55K. Interestingly, the interaction of E1A with DYRK1A and HAN11 appeared to play a role in suppression of transformation by activated Ras whereas interaction with CtBP was not necessary. This unexpected result suggests a need for revision of current models and provides new insight into transformation by the C terminus of E1A.

Laboratory support to Role 2 Afloat.

This article outlines the personal experiences of a biomedical scientist who recently deployed as a member of the Role 2 Afloat team on Exercise INTREPID DEFENDER. The laboratory support for the different departments is described and the provision of blood products available to Role 2 Afloat is outlined.