Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study.

OBJECTIVE: Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response. AIMS: To investigate if PD-L1 TPS ≥80%, smoking status or radiotherapy before or within 2 months of treatment influenced progression-free survival (PFS) in patients with NSCLC treated with pembrolizumab monotherapy. METHODS: PD-L1 TPS, smoking status and radiotherapy exposure were compared in patients with NSCLC in National Health Service (NHS) Tayside (n=100) treated with pembrolizumab monotherapy between 1 November 2017 and 18 February 2022. Survival estimates were compared using log-rank analysis, and Cox proportional hazards analysis was used to investigate the influence of potential confounding factors, including tumour stage and performance status. RESULTS: PFS was not significantly different (log-rank HR=0.330, p=0.566) comparing patients with PD-L1 TPS 50-79% and PD-L1 TPS ≥80%. Smokers had significantly improved PFS (log-rank HR=4.867, p=0.027), while patients receiving radiotherapy had significantly decreased PFS (log-rank HR=6.649, p=0.012). A Cox regression model confirmed that both radiotherapy (p=0.022) and performance status (p=0.009) were independent negative predictors of PFS. CONCLUSIONS: More rigorous PD-L1 TPS stratification did not influence survival outcomes. Smoking history improved PFS, although it was not an independent response predictor, while radiotherapy and performance status independently influenced clinical response. We suggest that further stratification of PD-L1 TPS is not warranted, while performance status and radiotherapy treatment may be additional clinically useful biomarkers of response to pembrolizumab in patients with NSCLC.

The Acceptability of a Recovery Group Intervention in Acute Inpatient Mental Health Wards.

The aim of the present study was to evaluate the feasibility and explore the service user experience of a recovery-focused group intervention delivered in acute inpatient wards in a National Health Service (NHS) Trust in England, United Kingdom. Feedback from the Recovery Group Questionnaire given to patients who had attended the Recovery Group whilst admitted to acute inpatient wards was collated and analysed. The results suggest that patients found the group useful and supportive, as well as easy to follow. Themes which emerged from the content analysis included, value, challenges, support and understanding. The feedback also showed that patients found having an Expert by Experience co-facilitating was beneficial. The Recovery Group is an acceptable and feasible group intervention for those who are admitted to acute inpatient wards. Further research examining the clinical effectiveness of the intervention may be considered, however there are some barriers to doing so given the open-access format of the group.

A relational investigation of Israeli gay fathers' experiences of surrogacy, early parenthood, and mental health in the context of the COVID-19 pandemic.

Perinatal distress affects approximately 10% of fathers, but little is known about how gay fathers experience the challenges surrounding childbirth and early parenting of a child. This study explored gay fathers' experiences of having a baby via transnational surrogacy, raising that baby as a gay parent, and the context of the COVID-19 pandemic. In-depth qualitative interviews were conducted with 15 Israeli men to understand their experiences of surrogacy and early parenthood, focusing on the impact on their mental health and the relational factors involved. Secondary narrative analysis revealed that fathers constructed surrogacy as a perilous quest that required strong intentionality to undertake. The first year of parenthood was conceptualised alternately as a joyful experience and/or one that challenged fathers' identities and mental health. A relational framework was applied to better conceptualise the fathers' narratives, revealing that actual connections-and the potentials for links-considerably shaped experiences of surrogacy, perinatal distress and recovery. Implications for research and policy are discussed.

How to interpret spinal imaging in paediatric trauma.

Spinal injuries in children are fortunately rare; however, it is important that they are assessed and managed in a timely manner. A systematic approach to traumatic spinal injuries should be used, by following recent evidence and national protocols, in order to avoid misinterpretation and potentially, inappropriate discharge. The aim of this article is to highlight the concepts of spinal imaging in paediatric trauma with regards to indications, interpretation and limitations.

Maori and Pacific people in New Zealand have a higher risk of hospitalisation for COVID-19.

AIMS: We aim to quantify differences in clinical outcomes from COVID-19 infection in Aotearoa New Zealand by ethnicity and with a focus on risk of hospitalisation. METHODS: We used data on age, ethnicity, deprivation index, pre-existing health conditions and clinical outcomes on 1,829 COVID-19 cases reported in New Zealand. We used a logistic regression model to calculate odds ratios for the risk of hospitalisation by ethnicity. We also considered length of hospital stay and risk of fatality. RESULTS: After controlling for age and pre-existing conditions, we found that Maori have 2.50 times greater odds of hospitalisation (95% CI 1.39-4.51) than non-Maori non-Pacific people. Pacific people have three times greater odds (95% CI 1.75-5.33). CONCLUSIONS: Structural inequities and systemic racism in the healthcare system mean that Maori and Pacific communities face a much greater health burden from COVID-19. Older people and those with pre-existing health conditions are also at greater risk. This should inform future policy decisions including prioritising groups for vaccination.

Estimated inequities in COVID-19 infection fatality rates by ethnicity for Aotearoa New Zealand.

AIMS: There is limited evidence as to how clinical outcomes of COVID-19 including fatality rates may vary by ethnicity. We aim to estimate inequities in infection fatality rates (IFR) in New Zealand by ethnicity. METHODS: We combine existing demographic and health data for ethnic groups in New Zealand with international data on COVID-19 IFR for different age groups. We adjust age-specific IFRs for differences in unmet healthcare need, and comorbidities by ethnicity. We also adjust for life expectancy reflecting evidence that COVID-19 amplifies the existing mortality risk of different groups. RESULTS: The IFR for Maori is estimated to be 50% higher than that of non-Maori, and could be even higher depending on the relative contributions of age and underlying health conditions to mortality risk. CONCLUSIONS: There are likely to be significant inequities in the health burden from COVID-19 in New Zealand by ethnicity. These will be exacerbated by racism within the healthcare system and other inequities not reflected in official data. Highest risk communities include those with elderly populations, and Maori and Pacific communities. These factors should be included in future disease incidence and impact modelling.

Security needs among patients referred for high secure care in Broadmoor Hospital England.

BACKGROUND: Security needs among patients referred to forensic mental health services have rarely been systematically studied. AIMS: To ascertain security needs among patients referred to a high secure hospital, Broadmoor High Secure Hospital, England. We also aimed to compare the security needs for those referred to mental illness services with those referred to personality disorder services in the hospital. METHOD: A retrospective complete cohort study of all referrals to Broadmoor Hospital over a 2-year period was conducted. All referred patients (n = 204) were assessed for need for high secure care by two Broadmoor clinicians. The final decision on need for admission was taken by a multidisciplinary admission panel. Independent of the panel, researchers rated need for security using the DUNDRUM-1 triage security scale. RESULTS: Those admitted to Broadmoor Hospital had higher triage security scores than those declined (F = 4.209, d.f. = 1, P = 0.042). Referrals to the personality disorder pathway had higher security needs than those referred to the mental illness pathway high secure service (F = 6.9835, d.f. = 1, P = 0.0089). Overall security needs among referrals to Broadmoor were extremely high, both by comparison with previous needs identified in UK medium secure services and international medium and high secure services. CONCLUSIONS: High secure patient cohorts represent a uniquely vulnerable group within mental health services, with extremely high security needs identified in this study. This has significant implications for services given the high levels of resources needed to provide therapeutically safe and secure care and treatment to this group.

Community forensic psychiatric services in England and Wales.

Forensic psychiatry is an established medical specialty in England and Wales. Although its origins lie in the 19th century, the development of secure hospitals accelerated in the late 20th century. Services for mentally disordered offenders in the community have developed most recently and it is these services, which are the focus of this article. We have looked broadly at community services and have included criminal justice liaison and diversion services in our remit. We have also considered partnerships between health and justice agencies as well as mental health and criminal legislation. We consider the limited research evidence in relation to community forensic services and the discussion this has provoked.

The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down Syndrome.

Copy number variations to chromosome 21 (HSA21) cause intellectual disability and Down Syndrome, but our understanding of the HSA21 genetic factors which contribute to fetal brain development remains incomplete. Here, we focussed on the neurodevelopmental functions for EURL (also known as C21ORF91, Refseq Gene ID:54149), a protein-coding gene at the centromeric boundary of the Down Syndrome Critical Region (DSCR) of HSA21. We report that EURL is expressed during human and mouse cerebral cortex development, and we report that alterations to EURL mRNA levels within the human brain underlie Down Syndrome. Our gene perturbation studies in mice demonstrate that disruptions to Eurl impair progenitor proliferation and neuronal differentiation. Also, we find that disruptions to Eurl impair the long-term positioning and dendritic spine densities of cortical projection neurons. We provide evidence that EURL interacts with the coiled-coil domain-containing protein CCDC85B so as to modulate ß-catenin levels in cells. Further, we utilised a fluorescent reporter (8xTOPFLASHd2EGFP) to demonstrate that disruptions to Eurl alter ß-catenin signalling in vitro as well as in vivo. Together, these studies highlight EURL as an important new player in neuronal development that is likely to impact on the neuropathogenesis of HSA21-related disorders including Down Syndrome.

Bacurd1/Kctd13 and Bacurd2/Tnfaip1 are interacting partners to Rnd proteins which influence the long-term positioning and dendritic maturation of cerebral cortical neurons.

BACKGROUND: The development of neural circuits within the embryonic cerebral cortex relies on the timely production of neurons, their positioning within the embryonic cerebral cortex as well as their terminal differentiation and dendritic spine connectivity. The RhoA GTPases Rnd2 and Rnd3 are important for neurogenesis and cell migration within the embryonic cortex (Nat Commun 4:1635, 2013), and we recently identified the BTB/POZ domain-containing Adaptor for Cul3-mediated RhoA Degradation family member Bacurd2 (also known as Tnfaip1) as an interacting partner to Rnd2 for the migration of embryonic mouse cortical neurons (Neural Dev 10:9, 2015). FINDINGS: We have extended this work and report that Bacurd1/Kctd13 and Bacurd2/Tnfaip1 are interacting partners to Rnd2 and Rnd3 in vitro. Given that these genes are expressed during cortical development, we performed a series of in utero electroporation studies in mice and found that disruptions to Bacurd1/Kctd13 or Bacurd2/Tnfaip1 expression impair the long-term positioning of E14.5-born cortical neurons within the postnatal (P17) mouse cerebral cortex. We also find that forced expression of Bacurd1/Kctd13 and Bacurd2/Tnfaip1 alters the branching and dendritic spine properties of layer II/III projection neurons. CONCLUSIONS: We identify Bacurd1/Kctd13 and Bacurd2/Tnfaip1 as interacting partners to Rnd proteins which influence the development of cortical neurons. Their neurodevelopmental functions are likely to be relevant to human brain development and disease.

Subjective experience of early imprisonment.

BACKGROUND: Some say 'prison works', others say that it only harms. Overall, longitudinal studies of prisoners suggest some positive impact on mental state, but post-release recidivism is high. How do men at high risk for repeated imprisonment experience it? AIM: To explore prison (gaol) experience among men awaiting trial in custody. METHODS: In a prospective longitudinal study, 170 men were interviewed just after reception about their social context and mental state and again three weeks later, when each was asked to describe his current prison experience; 75% had been in prison before. Data were analysed qualitatively and quantitatively. RESULTS: Each man had views on his imprisonment. Data were saturated after 20 interviews. The core concern was its overall emotional impact, in full negative to positive range, with recognition that this could and did change in either direction, both passively and through active processes. Underpinning themes were along the dimensions of missing people to asylum from the outside world; in-prison bullying to positive staff and/or inmate relationships; boredom to relief in routine; and 'doing my head in' to salvation from drug-induced decline. Testing the model in the whole sample confirmed no association between prison impact and pre-prison factors. Negative experience was associated with severe depression within but not before this imprisonment. More positive experience related to good in-prison relationships. CONCLUSIONS: During pre-trial custodial detention, there is a greater range of experience than generally previously reported. The simple expedients of prison staff developing good relationships with prisoners, and facilitating these between prisoners, could be life-saving. Highly positive experiences may be more an indictment on community services than an endorsement of imprisonment.

Unravelling the biology of human papillomavirus (HPV) related tumours to enhance their radiosensitivity.

HPV infection is associated with most squamous cell carcinomas (SCC) of the uterine cervix and many head and neck SCC. While recent understanding of the mechanisms of HPV-induced carcinogenesis has lead to the development of prophylactic vaccines, the principal modality of treatment is radiotherapy and despite concurrent chemotherapy, outcomes remain suboptimal. Improving the radiotherapeutic index thus remains an important challenge as well as defining predictive assays for treatment outcome of HPV-related tumours. Therefore elucidating the influence of the HPV virus on tumour radiosensitivity is of major interest due to the prevalence of HPV-related tumours worldwide and due to evidence that head and neck HPV-tumours have markedly different clinical outcomes compared to non-HPV-related tumours. This difference may allow for different treatment strategies to be developed. The present review aims to summarize the current understanding of radiosensitivity and HPV-related tumour biology in order to subsequently develop new approaches to enhance the therapeutic index. This review also emphasizes the relevance of E6 and E7 oncoproteins to tumour cell response to radiotherapy suggesting that specific targeted approaches such as concomitant modulation of additional pathways using targeted therapies should offer new therapeutic avenues.

An investigation into the role of spirituality in nursing.

This article examines spirituality in nursing in terms of a critical literature review. The literature suggests that there is an increasing demand for holistic care within the NHS. Holistic care is based on the idea that there should be a balance between body, mind and spirit, however, clinical experience suggests that the spiritual dimension of nursing is rarely considered as there is a focus on what is perceived as scientific professionalism. The aim of this article is to explore the nature of spiritual care, discuss whether there is a need for it in nursing and explore ways in which nurses can provide it. This article is based on a critical review of the literature and empirical data on spirituality in nursing and identifies contrasting opinions around the definition of spiritual nursing care. Nurses can provide spiritual care by being conscious of their own spirituality as well as that of patients.