Genomic investigations of unexplained acute hepatitis in children.

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

Patient and healthcare professionals' perceptions of a combined blood and faecal immunochemical test for excluding colorectal cancer diagnosis in primary care.

OBJECTIVES: To explore the perceptions of patients and healthcare professionals on Raman-faecal immunochemical test (FIT) as an alternative test for colorectal cancer exclusion in primary care. DESIGN: Semi-structured interviews within a feasibility study. SETTING: Patients presenting to primary care with colorectal symptoms and healthcare professionals working in primary and secondary care. PARTICIPANTS: A total of 23 patients and 12 healthcare professionals. METHODS: Patient participants were asked to complete a novel combined Raman-FIT test before being seen in secondary care. This study sought their opinions about the test. We also sought the views of healthcare professionals. FINDINGS: Patients and healthcare professionals agreed that Raman-FIT was a suitable test to be given in primary care. It aligned with routine practice and was a simple test for most patients to complete. CONCLUSIONS: Patients are willing and able to complete the Raman-FIT test in primary care. Raman-FIT may accelerate access to diagnosis with the potential to improve cancer outcomes. PATIENT AND PUBLIC INVOLVEMENT: Lay members (J. H. and I. H.) with experience and knowledge of colorectal cancer and screening contributed to developing, undertaking, and disseminating all aspects of the research. They were supported to collaborate as equal members of the research team. They were involved in developing the study as coapplicants, using personal experience to ensure that the research and its methods were relevant to the patient and public needs. Both prepared participant information sheets, coanalysed data, and contributed to study reporting and dissemination through papers, conference presentations and a lay summary.

Musical reward across the lifespan.

Music is ubiquitous. Despite the fact that most people find music enjoyable, there are individual differences in the degree to which listeners derive pleasure from music. However, there has been little focus on how musical reward may change across the lifespan. Some theories predict that there would be little change, or even an increase in musical reward across the lifespan, while others suggest that older adults may have decreased capacity for musical reward. Here, we investigated musical reward across the lifespan. Participants consisted of American adults ranging between 20-85 years old (n = 20 participants in each 10-year age bin). Participants in Study 1 completed the Barcelona Music Reward Questionnaire (BMRQ), which is a multi-dimensional assessment of musical reward. We found a negative correlation between age and BMRQ scores, suggesting decreases in musical reward across the lifespan. When investigating which components were driving this effect, we found that the music seeking subscale was the strongest predictor of age. Participants in Study 2 completed the Aesthetic Experiences in Music Scale (AES-M), which focuses on intense emotional responses to music. In contrast to the BMRQ, we found no relationship between age and scores on the AES-M, suggesting that strong emotional responses to music are consistent across the lifespan. These results have implications for the use of music as a therapeutic tool in older adults. In addition, this work points to the importance of considering age when investigating reward for music and suggests that the ways individuals experience music may change across the lifespan.

Hepatitis of unknown aetiology in children - epidemiological overview of cases reported in Europe, 1 January to 16 June 2022.

Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epidemiological, clinical and microbiological data available in TESSy. Of the reported cases, 77.3% were 5 years or younger and 53.5% had a positive test for adenovirus, 10.4% had a positive RT-PCR for SARS-CoV-2 and 10.3% were coinfected with both pathogens. Cases with adenovirus infections were significantly more likely to be admitted to intensive care or high-dependency units (OR = 2.11; 95% CI: 1.18-3.74) and transplanted (OR = 3.36; 95% CI: 1.19-9.55) than cases with a negative test result for adenovirus, but this was no longer observed when looking at this association separately between the UK and other countries. Aetiological studies are needed to ascertain if adenovirus plays a role in this possible emergence of hepatitis cases in children and, if confirmed, the mechanisms that could be involved.

EarLy Exercise in blunt Chest wall Trauma: a feasibility trial (ELECT Trial).

BACKGROUND: The aim was to complete a feasibility study that would test the methods of the main trial, that will investigate whether early thoracic and shoulder girdle exercises reduce chronic pain in patients with blunt chest wall trauma, when compared with normal care. METHODS: A single centre, parallel, feasibility randomised controlled trial was completed at a University Teaching Hospital in Wales between June and September 2019. Adult patients with blunt chest wall trauma, admitted to hospital for greater than 24 hours, with no concurrent, immediately life-threatening injuries, were included. The intervention was a simple physiotherapy programme comprising thoracic and shoulder girdle exercises. Feasibility outcome measures included: primary outcomes: (1) 80% or more of identified eligible patients were approached for potential recruitment to the trial (2) 30% or less of approached, eligible patients dissented to participate in the trial; secondary outcomes: (3) follow-up data for patient secondary outcomes can be collected for 80% or more of patients, (4) there should be no greater than 10% increase in serious adverse events in the intervention group compared with the control group. RESULTS: A total of 19/19 (100%) patients were deemed eligible for the trial and were approached for participation, 5/19 (26%) eligible patients declined to participate in the trial, follow-up data were collected for n=10/14 (71%) patients and there were no serious adverse events reported in either group. CONCLUSIONS: We have demonstrated that a fully powered randomised clinical trial of the EarLy Exercise in blunt Chest wall Trauma Trial is feasible. TRIAL REGISTRATION NUMBER: ISRCTN16197429.

Prognostic prediction tools and clinician communication: a qualitative study of the effect of the STUMBL tool on clinical practice.

BACKGROUND: In recent years, researchers and clinicians have been developing prognostic prediction tools (PPTs) as a way of identifying patients at risk of deterioration. The use of PPTs in the clinical environment not only impacts the risk of adverse outcomes for patients, but the use of these tools also effect clinical practice. Much attention has been paid to the clinical performance of PPTs. But more insight is needed on how the use of PPTs impacts clinical practice. The objective of this study was to map some of the ways in which PPTs effect clinical practice. The STUMBL (STUdy evaluating the impact of a prognostic model for Management of BLunt chest wall trauma patients) feasibility trial evaluated the use of a new prognostic prediction tool (PPT) to guide the management blunt chest wall trauma patients in the emergency departments (ED). The trial was undertaken between October 2016 and September 2018 and conducted at four sites in England and Wales. Nested within the feasibility trial was a qualitative study aimed at understanding how ED clinicians experienced and used the PPT. The qualitative methods included a focus group and telephone interviews with 9 ED clinicians. This study focused on participant perceptions of the feasibility and use of the STUMBL tool on clinical practice in the ED. RESULTS: Clinical practice is reshaped as a result of the introduction of the STUMBL PPT into the clinical environment. The PPT enhanced reflexive awareness of prognostic practice; facilitated communication between patients and professionals; helps to guide patient outcomes; and provides a common ground for clinician discussion on prognostication. CONCLUSIONS: The qualitative data collected offered useful insights into the ways in which the tool changes clinical practice. This was a small study of the effect of one kind of PPT on clinical practice. Nevertheless, this study maps areas in which clinical practice is affected by the introduction of a PPT into the clinical environment. More research is needed to better understand these effects, and to understand how these tools become embedded in clinical practice over the longer term.

Histone variant H3.3-mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos.

Derepression of chromatin-mediated transcriptional repression of paternal and maternal genomes is considered the first major step that initiates zygotic gene expression after fertilization. The histone variant H3.3 is present in both male and female gametes and is thought to be important for remodeling the paternal and maternal genomes for activation during both fertilization and embryogenesis. However, the underlying mechanisms remain poorly understood. Using our H3.3B-HA-tagged mouse model, engineered to report H3.3 expression in live animals and to distinguish different sources of H3.3 protein in embryos, we show here that sperm-derived H3.3 (sH3.3) protein is removed from the sperm genome shortly after fertilization and extruded from the zygotes via the second polar bodies (PBII) during embryogenesis. We also found that the maternal H3.3 (mH3.3) protein is incorporated into the paternal genome as early as 2 h postfertilization and is detectable in the paternal genome until the morula stage. Knockdown of maternal H3.3 resulted in compromised embryonic development both of fertilized embryos and of androgenetic haploid embryos. Furthermore, we report that mH3.3 depletion in oocytes impairs both activation of the Oct4 pluripotency marker gene and global de novo transcription from the paternal genome important for early embryonic development. Our results suggest that H3.3-mediated paternal chromatin remodeling is essential for the development of preimplantation embryos and the activation of the paternal genome during embryogenesis.

"How Long Have I Got?"-A Prospective Cohort Study Comparing Validated Prognostic Factors for Use in Patients with Advanced Cancer.

BACKGROUND: The optimal prognostic factors in patients with advanced cancer are not known, as a comparison of these is lacking. The aim of the present study was to determine the optimal prognostic factors by comparing validated factors. MATERIALS AND METHODS: A multicenter, prospective observational cohort study recruited patients over 18 years with advanced cancer. The following were assessed: clinician-predicted survival (CPS), Eastern Cooperative Oncology Group performance status (ECOG-PS), patient reported outcome measures (anorexia, cognitive impairment, dyspnea, global health), metastatic disease, weight loss, modified Glasgow Prognostic Score (mGPS) based on C-reactive protein and albumin, lactate dehydrogenase (LDH), and white (WCC), neutrophil (NC), and lymphocyte cell counts. Survival at 1 and 3 months was assessed using area under the receiver operating curve and logistic regression analysis. RESULTS: Data were available on 478 patients, and the median survival was 4.27 (1.86-7.03) months. On univariate analysis, the following factors predicted death at 1 and 3 months: CPS, ECOG-PS, mGPS, WCC, NC (all p < .001), dyspnea, global health (both p ≤ .001), cognitive impairment, anorexia, LDH (all p < .01), and weight loss (p < .05). On multivariate analysis ECOG-PS, mGPS, and NC were independent predictors of survival at 1 and 3 months (all p < .01). CONCLUSION: The simple combination of ECOG-PS and mGPS is an important novel prognostic framework which can alert clinicians to patients with good performance status who are at increased risk of having a higher symptom burden and dying at 3 months. From the recent literature it is likely that this framework will also be useful in referral for early palliative care with 6-24 months survival. IMPLICATIONS FOR PRACTICE: This large cohort study examined all validated prognostic factors in a head-to-head comparison and demonstrated the superior prognostic value of the Eastern Cooperative Oncology Group performance status (ECOG-PS)/modified Glasgow Prognostic Score (mGPS) combination over other prognostic factors. This combination is simple, accurate, and also relates to quality of life. It may be useful in identifying patients who may benefit from early referral to palliative care. It is proposed ECOG-PS/mGPS as the new prognostic domain in patients with advanced cancer.

The safety of intracytoplasmic sperm injection and long-term outcomes.

The pioneering of intracytoplasmic sperm injection (ICSI) approximately 25 years ago revolutionized the treatment of infertile couples. Today, ICSI remains an indispensable part of assisted reproductive treatments (ART) and has resulted in the birth of millions of babies. The 25th anniversary of ICSI marks a chronologic landmark in its evolving history. This landmark also serves as an opportunity to thoroughly appraise the safety of ICSI and analyze the long-term outcomes of ICSI-conceived children. In this review, we collate and analyze salient data accrued over the past 25 years pertaining to the long-term safety of ICSI and ICSI conceptions. We also evaluate the effects of ICSI on the perinatal outcomes, congenital malformation rates, cognitive development and reproductive health of ICSI-conceived neonates, children, adolescents and adults, respectively. In doing so, we also highlight the existence of potential confounders and biases that frequently obscure the interpretation of clinical follow-up studies.

Chronic kidney disease in an Aboriginal population: A nurse practitioner-led approach to management.

PROBLEM: Chronic kidney disease (CKD) is a significant health problem impacting Australia's Aboriginal and Torres Strait Islander population. After age adjustment, the prevalence of kidney disease is 3.7 times higher in Aboriginal people and 7.3 times higher for end-stage kidney disease compared with the wider population. Yet at an Aboriginal Community Controlled Health Service (ACCHS) with a significant patient population, fewer than expected numbers of Aboriginal patients were identified with CKD. DESIGN: The ACCHS engaged a nurse practitioner to lead a systematic approach to the identification and treatment of CKD. SETTING: This nurse practitioner-led approach to CKD was developed and implemented at a rural NSW ACCHS, with the support of a partnership formed between the nurse practitioner, the ACCHS, a nephrologist from a referral hospital and a statewide NGO. KEY MEASURES FOR IMPROVEMENT: The primary measure for improvement has been to identify and stage patients with CKD and establish management plans as appropriate. STRATEGIES FOR CHANGE: This nurse-led project was established to: (i) identify patients with CKD; (ii) provide access for CKD patients to appropriate services; (iii) commence pharmacological and non-pharmacological strategies that enable remission or regression of CKD; and (iv) educate practice GPs and other staff members on CKD clinical guidelines and best practice. EFFECTS OF CHANGE: The CKD project has improved access to essential health care for vulnerable and at-risk populations, with 187 patients to date having been identified with kidney disease and staged for its severity. LESSONS LEARNT: The need for strong multi-disciplinary teamwork has been demonstrated with good communication strategies implemented.

Patient and clinician perceptions of blunt chest trauma management and recovery: a qualitative study.

PURPOSE: To explore patient and clinician perceptions of blunt chest trauma management and recovery, when discharged directly home from the Emergency Department (ED). METHODS: This was a qualitative study, completed in a trauma unit in Wales. Blunt chest trauma was defined as an isolated blunt injury to the chest wall, resulting in bruising or rib fractures. Data collection involved semi-structured telephone interviews and focus groups with patients and clinicians respectively. Data analysis was completed using reflexive thematic coding. RESULTS: Twelve patient interviews and three focus groups (23 clinicians) were conducted. In the interviews, seven males and five females participated, with a mean age of 54 years (range 28-74). Clinicians included nurses, doctors, and therapists. Two main themes emerged; 1) the ED experience and 2) recovery once home; each with a number of sub-themes. Results highlighted the significant impact of pain on recovery, and that there is a disjuncture between organisational perspectives of clinicians, and the individual personal perspective of patients. DISCUSSION: Recovery from blunt chest trauma for patients discharged directly home from the ED is a challenging and complex process. Protocol-driven care does not always lead to good patient experience, as it focuses primarily on hospital services and resources.

Recovery from blunt chest trauma is a complex process, leading to poor outcomes including pain and disability.Protocol-driven care of blunt chest trauma does not always lead to a good patient experience.Patients with blunt chest trauma benefit from reassurance that their severity of pain is normal, prior to discharge home from the Emergency Department (ED).Education regarding pacing activity, rest, and reliance on others for a period of time following injury can lead to an improved recovery experience.

The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England.

The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.

Did the COVID-19 pandemic affect levels of burnout, anxiety and depression among doctors and nurses in Bangladesh? A cross-sectional survey study.

INTRODUCTION: COVID-19 has caused severe disruption to clinical services in Bangladesh but the extent of this, and the impact on healthcare professionals is unclear. We aimed to assess the perceived levels of anxiety, depression and burnout among doctors and nurses during COVID-19 pandemic. METHODS: We undertook an online survey using RedCap, directed at doctors and nurses across four institutions in Bangladesh (The Sheikh Russel Gastro Liver Institute & Hospital (SRNGIH), Dhaka Medical College Hospital (DMCH), Mugda Medical College Hospital (MMCH) and M Abdur Rahim Medical College (MARMC) Hospital). We collected information on demographics, awareness of well-being services, COVID-19-related workload, as well as anxiety, depression and burnout using two validated questionnaires: the Hospital Anxiety and Depression Scale (HADS) and the Maslach Burnout Inventory (MBI). RESULTS: Of the 3000 participants approached, we received responses from 2705 (90.2%). There was a statistically significant difference in anxiety, depression and burnout scores across institutions (p<0.01). Anxiety, depression and burnout scores were statistically worse in COVID-19 active staff compared with those not working on COVID-19 activities (p<0.01 for HADS anxiety and depression and MBI emotional exhaustion (EE), depersonalisation (DP) and personal accomplishment (PA)). Over half of the participants exhibited some level of anxiety (SRNGIH: 52.2%; DMCH: 53.9%; MMCH: 61.3%; MARMC: 68%) with a high proportion experiencing depression (SRNGIH: 39.5%; DMCH: 38.7%; MMCH: 53.7%; MARMC: 41.1%). Although mean burnout scores were within the normal range for each institution, a high proportion of staff (almost 20% in some instances) were shown to be classified as experiencing burnout by their EE, DP and PA scores. CONCLUSION: We identified a high prevalence of perceived anxiety, depression and burnout among doctors and nurses during the COVID-19 pandemic. This was worse in staff engaged in COVID-19-related activities. These findings could help healthcare organisations to plan for future similar events.

Is Panton-Valentine leucocidin (PVL) toxin associated with poor clinical outcomes in patients with community-acquired Staphylococcus aureus bacteraemia?

Introduction. Panton-Valentine leucocidin (PVL) toxin is a potential determinant of virulence associated with S. aureus infection.Gap Statement. The contribution of PVL to S. aureus pathogenicity remains unclear.Aim. To compare clinical outcomes in hospitalized patients with PVL-positive and PVL-negative community-acquired (CA) S. aureus bacteraemia.Methods. Three national datasets were combined to provide clinical and mortality data for patients with CA S. aureus blood culture isolates sent to the UK reference laboratory for PVL testing, August 2018 to August 2021. Multivariable logistic regression models were built for the effect of PVL positivity on 30 day all-cause mortality and 90 day readmission.Results. In 2191 cases of CA S. aureus bacteraemia, there was no association between PVL and mortality (adjusted odds ratio, aOR: 0·90, 95 % confidence interval, CI: 0·50-1·35, P=0·602) and no difference in median LOS (14 versus 15 days, P=0.169). PVL-positive cases had lower odds of readmission (aOR 0·74, CI 0·55-0.98, P=0·038). There was no evidence that MRSA status modified this effect (P=0·207).Conclusions. In patients with CA S. aureus bacteraemia PVL toxin detection was not associated with worse outcomes.

Demonstrating the learning and impact of embedding participant involvement in a pandemic research study: the experience of the SARS-CoV-2 immunity & reinfection evaluation (SIREN) study UK, 2020-2023.

BACKGROUND: Participant involvement in research studies is not a new concept, yet barriers to implementation remain and application varies. This is particularly true for pandemic response research studies, where timeframes are condensed, pressure is high and the value and inclusion of participant involvement can be overlooked. The SIREN Participant Involvement Panel (PIP) provides a case study for participant involvement in pandemic research, working in partnership with people who the research is for and about. METHODS: SIREN and the British Society for Immunology (BSI) recruited and ran two phases of the PIP, involving 15 members in total over a 16-month period. Phase 1 ran between January and August 2022 and Phase 2 between October 2022 and March 2023. Activity figures including recruitment interest and PIP meeting attendance were recorded. To evaluate how the PIP has influenced SIREN, feedback was collected from (a) researchers presenting at the PIP and (b) PIP members themselves. Evaluation at the end of Phase 1 informed our approach to Phase 2. Thematic grouping was planned to identify key lessons learned. RESULTS: Applications increased from n = 30 to n = 485 between Phase 1 and Phase 2 of the PIP, a more than 15-fold increase. The SIREN PIP positively impacted the design, implementation and evaluation phases of the study and sub-studies. Feedback from PIP members themselves was positive, with members highlighting that they found the role rewarding and felt valued. Learnings from the PIP have been condensed into five key themes for applying to future pandemic response research studies: the importance of dedicated resources; recruiting the right panel; understanding motivations for participant involvement; providing flexible options for involvement and enabling the early involvement of participants. CONCLUSIONS: The SIREN PIP has demonstrated the value of actively involving people who research is for and about. The PIP has provided an active feedback mechanism for research and demonstrated a positive influence on both SIREN study researchers and PIP members themselves. This paper makes the case for participant involvement in future pandemic research studies. Future work should include improved training for researchers and we would support the development of a national PIP forum as part of future pandemic research preparedness.

The SARS-Cov2 Immunity & Reinfection Evaluation (SIREN) study was set-up at speed during the early stages of the pandemic to help answer key questions about COVID-19 and inform the national pandemic response. It has provided valuable insight into COVID-19 infections, reinfections, and how well the vaccines work. SIREN helped to find these answers by regularly testing over 44,000 healthcare staff working at 135 NHS organisations. To support participant retention, SIREN established a Participant Involvement Panel (PIP) involving 15 SIREN participants to date. PIP members provide guidance and feedback to SIREN researchers on key research priorities, changes to the study and strategies for maximising participant engagement. This paper provides insight into how the PIP was set-up, run and the resources required from the perspective of the PIP and SIREN researchers. Lessons learned from establishing the PIP are summarised to help inform future pandemic response research studies. The paper adds to the evidence base, and makes the case for, the valuable role participant involvement can play in pandemic response research studies.

A novel blood based triage test for colorectal cancer in primary care: a pilot study.

BACKGROUND: The majority of colorectal cancers (CRCs) are detected after symptomatic presentation to primary care. Given the shared symptoms of CRC and benign disorders, it is challenging to manage the risk of missed diagnosis. Colonoscopy resources cannot keep pace with increasing demand. There is a pressing need for access to simple triage tools in primary care to help prioritise patients for referral. AIM: To evaluate the performance of a novel spectroscopy-based CRC blood test in primary care. DESIGN & SETTING: Mixed-methods pilot study of test performance and GP focus group discussions in South Wales. METHOD: Patients on the urgent suspected cancer (USC) pathway were recruited for the Raman spectroscopy (RS) test coupled to machine learning classification ('Raman-CRC') to identify CRC within the referred population. Qualitative focus group work evaluated the acceptability of the test in primary care by thematic analysis of focus group theorising. RESULTS: A total of 532 patients aged ≥50 years referred on the USC pathway were recruited from 27 GP practices. Twenty-nine patients (5.0%) were diagnosed with CRC. Raman-CRC identified CRC with sensitivity 95.7%, specificity 69.3% with area under curve (AUC) of 0.80 compared with colonoscopy as the reference test (248 patients). Stage I and II cancers were detected with 78.6% sensitivity. Focus group themes underlined the convenience of a blood test for the patient and the test's value as a risk assessment tool in primary care. CONCLUSION: The findings support this novel, non-invasive, blood-based method to prioritise those patients most likely to have CRC. Raman-CRC may accelerate access to diagnosis with potential to improve cancer outcomes.

Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes. METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups. FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (ß 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity. INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation. FUNDING: None.

Views of Care at End of Life: A Secondary Analysis of Online Feedback Using Care Opinion.

Although there are studies on the use of social media and palliative and end-of-life care (PEOLC), there are no studies specifically investigating the content of online public feedback about PEOLC services. This study sought to understand experiences of end-of-life care provided in hospitals in the West of Scotland by exploring the main themes within the content of stories posted on a nationally endorsed nonprofit feedback online platform, Care Opinion, within a 2-year period. We used "Appreciative Inquiry" as a theoretical framework for this study to determine what works well in end-of-life care, while also identifying areas for further improvement. Of the 1428 stories published on "Care Opinion" from March 2019 to 2021 regarding hospitals in the West of Scotland, 48 (3.36%) were related to end-of-life care, of which all were included in data analysis. Using the software package NVivo and thematic analysis, we identified 4 key themes. We found that people overwhelmingly posted positive feedback about their experiences with end-of-life care. People reported positively about staff professionalism in providing compassionate and person-centered care to meet their loved ones needs at end of life. Other experiences of care related to challenges facing healthcare services, particularly during the COVID-19 pandemic. Quality appraisal of staff responses highlighted areas for improving feedback. This study can add to the aim of improving staff response to people's concerns about end-of-life care. This study has provided a novel perspective of patients' experiences of end-of-life care in hospitals in the West of Scotland. Novel insights were the appreciation of quality of care, staff professionalism, effective communication, and meeting patient's needs at end-of-life particularly by nursing staff.

Patient-Reported Experiences and Satisfaction with Rural Outreach Clinics in New South Wales, Australia: A Cross-Sectional Study.

Introduction: Many studies have been conducted on how physicians view outreach health services, yet few have explored how rural patients view these services. This study aimed to examine the patient experience and satisfaction with outreach health services in rural NSW, Australia and the factors associated with satisfaction. Methods: A cross-sectional study was conducted among patients who visited outreach health services between December 2020 and February 2021 across rural and remote New South Wales, Australia. Data on patient satisfaction were collected using a validated questionnaire. Both bivariate (chi-squared test) and multivariate analyses (logistic regression) were performed to identify the factors associated with the outcome variable (patient satisfaction). Results: A total of 207 participants were included in the study. The mean age of respondents was 58.6 years, and 50.2% were men. Ninety-three percent of all participants were satisfied with the outreach health services. Respectful behaviours of the outreach healthcare practitioners were significantly associated with the higher patient satisfaction attending outreach clinics. Conclusions: The current study demonstrated a high level of patient satisfaction regarding outreach health services in rural and remote NSW, Australia. Further, our study findings showed the importance of collecting data about patient satisfaction to strengthen outreach service quality.

Sunproofed study protocol: A mixed-methods scoping study of sun safety policies in primary schools in Wales.

BACKGROUND: Skin cancer, including melanoma and non-melanoma (keratinocyte), is increasing in incidence in the UK. Accounting for half of all cancers in England and Wales, the disease significantly impacts overstretched dermatology services. Research suggests that 86% of melanoma is preventable with modified sun exposure. Educating children about sun safety in schools can help prevent skin cancer and is recommended by major health organisations. In England, teaching sun safety in primary schools is compulsory, while in Wales this is left to school discretion. AIMS: Understand how primary schools in Wales are responding to growing skin cancer rates and explore the effectiveness of sun safety policies in schools on knowledge and behaviour. METHODS: Sunproofed is a mixed-methods scoping study comprising 5 work packages (WP) using survey and routine electronic health record (EHR) data supplemented by qualitative case studies. Objective(s) are to: WP1: Discover if primary schools in Wales have sun safety policies; policy characteristics; determine factors that may influence their presence and identify areas where schools need support. WP2: Determine what EHR data is available regarding the incidence of sunburn in primary school children and the feasibility of using this data to evaluate the impact of sun safety policies. WP3: Understand the impact of sun safety policies on sun-safe knowledge and behaviour amongst children, parents, teachers, and school management; identify barriers and facilitators to schools implementing sun safety policies. WP4: Co-produce guidance regarding sun safety policies and best methods for implementation in schools. WP5: Disseminate guidance and findings widely to ensure impact and uptake. DISCUSSION: Skin cancer rates are increasing in the UK, straining limited resources. Sunproofed has the potential to inform the development of future prevention activities, both in Wales and beyond. This could reduce the number of skin cancer cases in the future and keep people healthier for longer.