Peer supporters' mental health and emotional wellbeing needs: Key factors and opportunities for co-produced training.

INTRODUCTION: Peer supporters are a valuable asset to mental health and support services, but their own mental health needs are often overlooked in research and practice. This study explored peer supporters' perceived challenges of maintaining their mental health and emotional wellbeing and co-produced training needs. METHODS: A qualitative approach was used to explore factors affecting peer supporters' mental health and emotional wellbeing. Semi-structured interviews and focus groups were conducted online with 11 peer supporters across North East England. RESULTS: A thematic analysis identified: 'Lack of training and support', 'Role ambiguity' and 'Emotional labour' as challenges experienced by peer supporters in relation to maintaining their mental health and emotional wellbeing. Peer supporters' own lived experiences had the potential to act as a barrier towards providing support to others. Conflict with peer 'supportees' sometimes negatively impacted on the peer supporter experience. Participant responses emphasised a need for person-centred, co-produced training. CONCLUSION: This work highlights the need for targeted training for peer supporters, including both role-specific education and strategies to support their mental health and emotional wellbeing. PATIENT OR PUBLIC CONTRIBUTION: Participants were contacted and asked to provide feedback on finalised themes to ensure the analysis was congruent with their experiences, further enabling the future development of an emotional wellbeing training programme for peer supporters.

You clapped, you cheered, but did anybody hear? A mixed-methods systematic review of dementia homecare workers' training and psychosocial needs.

The homecare sector's high turnover rate is linked to poor working conditions and a lack of person-centered practice. Limited research exists on the training and psychosocial needs of homecare workers caring for people living with dementia (PLWD). This systematic review explored these needs and identified 285 studies, of which seven studies met the inclusion criteria. A narrative synthesis identified four themes: "training and education challenges and facilitators;" "social isolation and the importance of peer support;" "emotional attachments and distress experienced by homecare workers;" and "working with families and its emotional impact on homecare workers." This review highlights the unmet educational and psychosocial needs of homecare workers and the negative impacts these unmet needs have. To improve person-centered practice in homecare, workers require dementia-specific training, and concurrent emotional and peer support, alongside support managing relationships with clients' families. Future research is required to implement an intervention to meet these needs.

Evaluating the effects of a multicomponent support service for people recently diagnosed with dementia and their carers: A qualitative study.

INTRODUCTION: Although prior research has provided an understanding of the needs of people living with dementia (PLWD) and their carers, less is known about how tailored multicomponent interventions impact their lives. This study explored the effect of providing ongoing support to people who had been recently diagnosed with dementia and to their carers. METHODS: We conducted interviews with a convenience sample of key stakeholders: 11 interviews with people who had dementia and their familial carers (n = 14) and six interviews with staff and other practitioners involved with the service (n = 13). Inductive thematic analysis was performed on the data. RESULTS: Four themes were developed: the service as a source of respite, peer support, activities as facilitators of emotional wellbeing, and social support. The service was well-respected, credible, and trusted and was highly valued by practitioners, clients, and carers. It had a clear role in supporting PLWD and their carers. Peer support provided through the service contributed to greatly reducing self-reported carer burden. CONCLUSION: Recommendations arising from this study include offering holistic services to PLWD and their carers, developing activities for men, raising awareness of services among practitioners working with PLWD, and improving partnerships between services and agencies working with older people. PATIENT OR PUBLIC CONTRIBUTION: Service users were consulted on the themes generated from the data and were asked to provide feedback to help guide the interpretation of the data and ensure this reflected their views and experiences.

Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses.

Glioblastoma multiforme (GBM) is the most common adult primary brain malignancy, with dismal survival rates of ~14.6 months. The current standard-of-care consists of surgical resection and chemoradiotherapy, however the treatment response is limited by factors such as tumour heterogeneity, treatment resistance, the blood-brain barrier, and immunosuppression. Several immunotherapies have undergone clinical development for GBM but demonstrated inadequate efficacy, yet future combinatorial approaches are likely to hold more promise. Olaparib is FDA-approved for BRCA-mutated advanced ovarian and breast cancer, and clinical studies have revealed its utility as a safe and efficacious radio- and chemo-sensitiser in GBM. The ability of Olaparib to enhance natural killer (NK) cell-mediated responses has been reported in prostate, breast, and lung cancer. This study examined its potential combination with NK cell therapies in GBM by firstly investigating the susceptibility of the GBM cell line T98G to NK cells and, secondly, examining whether Olaparib can sensitise T98G cells to NK cell-mediated responses. Here, we characterise the NK receptor ligand profile of T98G cells and demonstrate that Olaparib does not dampen T98G susceptibility to NK cells or elicit immunomodulatory effects on the function of NK cells. This study provides novel insights into the potential combination of Olaparib with NK cell therapies for GBM.

The Influence of MicroRNA-31 on Oxidative Stress and Radiosensitivity in Pancreatic Ductal Adenocarcinoma.

Radioresistance remains a significant challenge in treating pancreatic ductal adenocarcinoma (PDAC), contributing to the poor survival rates of this cancer. MicroRNAs (miRs) are small non-coding RNA molecules that may play an essential role in regulating radioresistance by altering the levels of oxidative stress. In this study, we investigated the role and potential mechanisms linking miR-31 to PDAC radioresistance. A pCMV-miR vector containing a miR-31 mimic was stably expressed into a miR-31-deficient PDAC cell line, BxPC-3. Additionally, a pmiRZip lentivector suppressing miR-31 was stably expressed in a miR-31 abundant PDAC cell line, Panc-1. Clonogenic assays were conducted to explore the role of miR-31 manipulation on radiosensitivity. Fluorometric ROS assays were performed to quantify ROS levels. The expression of potential miR-31 targets was measured by Western blot analysis. It was found that the manipulation of miR-31 altered the radiosensitivity in PDAC cells by regulating oxidative stress. Using online bioinformatics tools, we identified the 3'UTR of GPx8 as a predicted target of miR-31. Our study demonstrates, for the first time, that manipulating miR-31 alters GPx8 expression, regulating ROS detoxification and promoting either a radioresistant or radiosensitive phenotype. MiR-31 may represent a promising therapeutic target for altering radiosensitivity in PDAC cells.

Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel). A systematic review was conducted in accordance with PRISMA standards in July 2020. Individualized search strategies for three academic databases identified 5,885 studies between the years 1973 and 2020. After two rounds of screening, 250 studies were included. Data were extracted and assessed for bias. A multivariate three-level meta-analysis with subgroup moderators was run in R using AUC values as effect size. On the basis of this model, the pooled AUC value for all multi-biomarker panels (AUC = 0.898; 95% confidence interval (CI): 0.88-0.91) was significantly higher than all single biomarkers (AUC = 0.803; 95% CI: 0.78-0.83; P < 0.0001). The pooled AUC value for CA19-9 alone was significantly lower compared with the multi-biomarker panels containing CA19-9 (P < 0.0001). For the novel biomarkers, the pooled AUC for single biomarkers was also significantly lower compared with multi-biomarker panels (P < 0.0001). Novel biomarkers that have been repeatedly examined across the literature, such as TIMP-1, CEA, and CA125, are highlighted as promising. These results suggest that CA19-9 may be best used as an addition to a panel of biomarkers rather than alone, and that multi-biomarker panels generate the most robust results in blood-based PDAC diagnosis. Significance: In a systematic review and three-level multivariate meta-analysis, it is shown for the first time that blood-based multi-biomarker panels for the diagnosis of PDAC exhibit superior performance in comparison with single biomarkers. CA19-9 is demonstrated to have limited utility alone, and to perform poorly in patient control cohorts of both healthy and benign individuals. Multi-biomarker panels containing CA19-9 produce the best diagnostic performance overall.

Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?

Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using "liquid biopsies" to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.

Multi-Omic Biomarkers as Potential Tools for the Characterisation of Pancreatic Cystic Lesions and Cancer: Innovative Patient Data Integration.

Pancreatic cancer (PC) is regarded as one of the most lethal malignant diseases in the world, with GLOBOCAN 2020 estimates indicating that PC was responsible for almost half a million deaths worldwide in 2020. Pancreatic cystic lesions (PCLs) are fluid-filled structures found within or on the surface of the pancreas, which can either be pre-malignant or have no malignant potential. While some PCLs are found in symptomatic patients, nowadays many PCLs are found incidentally in patients undergoing cross-sectional imaging for other reasons-so called 'incidentalomas'. Current methods of characterising PCLs are imperfect and vary hugely between institutions and countries. As such, there is a profound need for improved diagnostic algorithms. This could facilitate more accurate risk stratification of those PCLs that have malignant potential and reduce unnecessary surveillance. As PC continues to have such a poor prognosis, earlier recognition and risk stratification of PCLs may lead to better treatment protocols. This review will focus on the importance of biomarkers in the context of PCLs and PCand outline how current 'omics'-related work could contribute to the identification of a novel integrated biomarker profile for the risk stratification of patients with PCLs and PC.

Energy compensation in enterally fed children.

Limited exposure to solid food in early childhood may affect the development of appetite regulation. We used formal satiation studies to assess energy compensation in children who have been artificially fed. Subjects were 11 children, median age 4.5 years (range 1-10) who were formerly (n=4) or currently (n=5) mainly tube fed or supplement fed (n=2), with a range of surgical or neurodevelopmental problems. On 2 separate days a high-energy preload (HEP) and low-energy preload (LEP) drink were given followed by a multi-item test lunch. A compensation index (COMPX) score was derived as follows: COMPX (%)=[(Meal(lep)-Meal(hep))/(Preload(hep)-Preload(lep))]× 100. The median (range) COMPX of the participants was 70% (-73% to 178%). The 8 boys tended to compensate more (median 99%) than the 3 girls (30%; P Mann-Whitney=0.1), but there was no clear association of compensation with age. Although a small preliminary study, this suggests that children who have been artificially fed demonstrate energy compensation comparable to that of normally fed children.

Present and future treatment strategies for pulmonary arterial hypertension : focus on phosphodiesterase-5 inhibitors.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare progressive disorder historically associated with mortality in <3 years post-diagnosis. The etiology of PAH is complex, multifactorial, and likely involves the interplay between genetic and environmental factors. These are reviewed with emphasis on the nitric oxide pathway. Use of treatment modalities including vasodilator therapy have resulted in improved symptoms, hemodynamics, and survival in these patients. Vasodilators, including the calcium channel antagonists, prostanoids, and endothelin receptor antagonists, have been used to counteract potential imbalances in vasoactive mediators in PAH patients; all have produced improved long-term symptomatology and hemodynamics. Only the prostanoid epoprostenol has improved survival in IPAH patients. Although these medications have worked well in many patients with PAH, each of them has limitations. The phosphodiesterase-5 (PDE-5) inhibitors are a relatively new form of treatment for PAH. They are designed to potentiate the effects of cyclic guanosine monophosphate, thereby mimicking endogenous nitric oxide within the vasculature. PDE-5 inhibitors are selective pulmonary vasodilators effective in animal models of pulmonary hypertension. The published clinical studies evaluating their use have been small in size to date but appear to demonstrate benefit. The recently completed 12-week randomized placebo-controlled Sildenafil Use in Pulmonary Hypertension (SUPER-1) trial demonstrated improvement in 6-minute walk distance and hemodynamics in patients receiving sildenafil. These data suggest that the PDE-5 inhibitors are effective in treating PAH and that it is likely that their usage will increase over time. The purpose of this review is to present a current view of the pathogenesis and treatment of PAH, with an emphasis on the use of PDE-5 inhibitors in these patients.

Quality of Internet geriatric health information: the GeriatricWeb project.

Many physicians report that Internet health information can affect their clinical decisions. Much of Internet geriatric health information (IGHI) is not controlled for quality, and there is no available process to assess the quality of IGHI used in clinical practice or in medical education. The objective of this project was to describe the development of an assessment process of IGHI and to report on the quality of existing IGHI through the GeriatricWeb project. The assessment was a trilevel process: identification, screening, and peer review. Medical librarians completed the identification of resources, and geriatric specialists conducted the screening and peer review. The peer-review process was accomplished using a developed tool (4 domains: credibility, accuracy, design, educational features; score 0-100, favorable assessment score > or = 75). More than 5,000 IGHI resources were identified, and 1,142 (22%) were advanced for screening. Of those, 246 (21%) were already peer reviewed, and 354 (31%) were advanced for peer review. Of those, 181 (51% or 20% of all those advanced for screening excluding those already peer reviewed) had a favorable assessment. Poor credibility and educational features contributed to this low quality. IGHI authored by national, federal, or academic organizations and targeted to higher academic levels was more likely to have a favorable assessment (P=0.01). Much publicly available IGHI is of suboptimal quality, particularly with regard to credibility and educational domains. Healthcare professionals need to be aware of how to locate high-quality IGHI and how to assess the quality of available IGHI.

Effect of an individualized treatment protocol on restoration of competency in pretrial forensic inpatients.

In this study, we evaluated the effectiveness of individualized treatment on restoration of competency in patients adjudicated incompetent to stand trial. Treatment groups included deficit-focused remediation (six individual sessions and four group sessions; n = 8), legal rights education (control group; six individual sessions and four group sessions; n = 10), and standard hospital treatment (control group; four group sessions; n = 8). There were no significant baseline differences among groups. All groups differed significantly on competency measures obtained before and after testing. The deficit-focused remediation and the legal rights education groups both demonstrated significantly higher post-treatment scores on competency measures than the standard hospital treatment group. Both groups demonstrated approximately 50 percent more improvement on the competency measures than the standard hospital treatment group. There were no significant differences between the deficit-focused remediation and legal rights education groups on post-test competency scores, suggesting that focus on individual deficits may not be a useful treatment strategy. Results demonstrate, however, that more frequent legal rights education is a worthwhile endeavor in treatment of incompetency.