Using volunteers to improve access to community rehabilitation in palliative care: the St Christopher's Living Well at Home Team.

Background: UK hospices often provide outpatient rehabilitation services for people with advanced progressive illness. However, some people are unable to travel, leading to inequity in rehabilitation access. Objectives: The Living Well at Home Team (LWAHT) at St Christopher's Hospice aimed to evaluate whether using volunteers to support rehabilitation in peoples' homes improved the reach of rehabilitation for people living in underserved localities and if it supported people to optimise their functional independence. Methods: This service improvement project evaluated hospice rehabilitation uptake during the implementation of volunteer-supported community rehabilitation. Following assessment by an LWAHT therapist, eligible people were matched with a trained volunteer who supported four to eight rehabilitation sessions in the person's home. The evaluation assessed uptake of the rehabilitation sessions. Mobility, wellbeing, and goal attainment outcomes were assessed by the Life-Space Assessment (LSA), General Health Questionnaire (GHQ), and Goal Attainment Scale (GAS), respectively. Results: In the first year, 183 patients were referred to the LWAHT; 123 were assessed and 96 received rehabilitation including 56 who were matched with a volunteer. Following volunteer support, patients reported significant improvements in mobility [LSA median 20 (IQR, 3.5-27.8)], general health [GHQ -2 (-5.25 to 0)], and achievement of goals [GAS T-score +8 (0-18.4)]. Conclusions: It was feasible to support community rehabilitation using hospice volunteers for people with advanced progressive illness. The LWAHT service also increased the uptake of hospice centre-based rehabilitation. Further work should test efficacy and identify patients requiring additional professional input. Key message: This is the first known study reporting on the use of trained rehabilitation volunteers to extend the reach of hospice rehabilitation services. People with limited access to the hospice, because of geographical location or personal circumstances, valued and benefited from tailored rehabilitation supported by the volunteers in their own homes.

Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery.

OBJECTIVE: To investigate postoperative functional connectivity (FC) alterations across impaired cognitive domains and their causal relationships with systemic inflammation. BACKGROUND: Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether FC alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remains unclear. METHODS: Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for tumor necrosis factor-a and interleukin-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations, and cytokines. RESULTS: Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC FC with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased tumor necrosis factor-a and decreased executive function up to day 7 after cardiac surgery. CONCLUSIONS: The decreased FC of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits after cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.

Early diagnosis of symptomatic ovarian cancer in primary care in the UK: opportunities and challenges.

BACKGROUND: Ovarian cancer is the sixth most common cause of cancer-related death in the UK amongst women. Ovarian cancer presents particular challenges for general practitioners (GPs) to diagnose due to its rarity and presentation with non-specific symptoms. METHODS: A narrative overview of the literature was conducted by searching PubMed and Researchgate for relevant articles, using keywords such as "ovarian cancer," "primary care" and "diagnosis." RESULTS AND DISCUSSION: Studies have shown that in the UK, GPs have a lower readiness to refer and investigate potential cancer symptoms compared with their international counterparts; and this has been correlated with reduced survival. Early diagnosis can be facilitated through a people-focussed and system-based approach which involves both educating GPs and using risk algorithms, rapid diagnostic centres/multi-disciplinary centres and being data-driven through the identification of best practice from national audits. Further research is required into the best evidence-based early investigations for ovarian cancer and more effective biomarkers.

N6-methyladenosine modulates long non-coding RNA in the developing mouse heart.

Long non-coding RNAs (lncRNAs) were reported to potentially play a regulatory role in the process of myocardial regeneration in the neonatal mouse. N6-methyladenosine (m6A) modification may play a key role in myocardial regeneration in mice and regulates a variety of biological processes through affecting the stability of lncRNAs. However, the map of m6A modification of lncRNAs in mouse cardiac development still remains unknown. We aimed to investigate the differences in the m6A status of lncRNAs during mouse cardiac development and reveal a potential role of m6A modification modulating lncRNAs in cardiac development and myocardial regeneration during cardiac development in mice. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) of the heart tissue in C57BL/6 J mice at postnatal day 1 (P1), P7 and P28 were performed to produce stagewise cardiac lncRNA m6A-methylomes in a parallel timeframe with the established loss of an intrinsic cardiac regeneration capacity and early postnatal development. There were significant differences in the distribution and abundance of m6A modifications in lncRNAs in the P7 vs P1 mice. In addition, the functional role of m6A in regulating lncRNA levels was established for selected transcripts with METTL3 silencing in neonatal cardiomyocytes in vitro. Based on our MeRIP-qPCR experiment data, both lncGm15328 and lncRNA Zfp597, that were not previously associated with cardiac regeneration, were found to be the most differently methylated at P1-P7. These two lncRNAs sponged several miRNAs which further regulated multiple mRNAs, including some of which have previously been linked with cardiac regeneration ability. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that differential m6A modifications were more enriched in functions and cellular signalling pathways related to cardiomyocyte proliferation. Our data suggested that the m6A modification on lncRNAs may play an important role in the regeneration of myocardium and cardiac development.

Systematic Review and Metaanalysis of the Reproducibility of Patient Self-reported Joint Counts in Rheumatoid Arthritis.

OBJECTIVE: To assess the reproducibility of patient-reported tender (TJCs) and swollen joint counts (SJCs) of patients with rheumatoid arthritis (RA) compared to trained clinicians. METHODS: We conducted a systematic literature review and metaanalysis of studies comparing patient-reported TJCs and/or SJCs to clinician counts in patients with RA. We calculated pooled summary estimates for correlation. Agreement was compared using a Bland-Altman approach. RESULTS: Fourteen studies were included in the metaanalysis. There were strong correlations between clinician and patient TJCs (0.78, 95% CI 0.76-0.80), and clinician and patient SJCs (0.59, 95% CI 0.54-0.63). TJCs had good reliability, ranging from 0.51 to 0.85. SJCs had moderate reliability, ranging from 0.28 to 0.77. Agreement for TJCs reduced for higher TJC values, suggesting a positive bias for self-reported TJCs, which was not observed for SJCs. CONCLUSION: Our metaanalysis has identified a strong correlation between patient- and clinician-reported TJCs, and a moderate correlation for SJCs. Patient-reported joint counts may be suitable for use in annual review for patients in remission and in monitoring treatment response for patients with RA. However, they are likely not appropriate for decisions on commencement of biologics. Further research is needed to identify patient groups in which patient-reported joint counts are unsuitable.

A quantitative study of letters to the editor by medical students in medical education journals.

Letters to the Editor offer ways for readers to engage with authors' publications. Letters are the shortest manuscript for medical students to publish and medical-education journals are best suited. The UK Foundation Programme rewards medical students achieving PubMed ID publications and we hypothesise that this is a main motivation for medical students to submit Letters to the Editor. A review of 15 medical-education journals with an impact factor was conducted to identify numbers and percentages of Letters to the Editor by medical students between July 2018 and June 2020. Affiliation of medical students was collected. Our results show over two years, 299 letters were published by medical students equating to 45.9% of total letters. There was a 60% overall increase in letters by medical students published in the first 12 months compared to second 12 months. During this period overall numbers of letters published increased by 27%. 86% of the letters published by medical students over the two-year period were from UK medical schools. Five schools accounted for 60.5% of these letters. The three medical schools with highest numbers of letters published were King's College London, Imperial College London and University of Oxford for both 2018/19 and 2019/20. The increase in letters published overall with greater numbers published by students, may indicate greater awareness of Letters to the Editor as means of dissemination amongst medical students. UK medical schools published large numbers of letters, perhaps reflecting increasing importance to students of publications due to impacting on subsequent jobs. Results from our quantitative research revealing: large numbers of letters by medical students, increase in letters published from 2018/19 to 2019/20 and overrepresentation of UK medical students supports the hypothesis that medical students are publishing letters to achieve PubMed IDs. Further qualitative research is required to test our hypothesis.

Anesthetics or anesthetic techniques and cancer surgical outcomes: a possible link.

As of 2018 cancer is responsible for almost 9.6 million deaths annually and, with an aging population, the incidence of cancer is expected to continue to rise. Surgery is an important treatment modality for patients with solid organ cancers. It has been postulated that, due to potentially overlapping processes underlying the development of malignancy and the therapeutic pathways of various anesthetic agents, the choice of anesthetic type and method of administration may affect post-operative outcomes in patients with cancer. This is a literature review of the most recent evidence extracted from various databases including PubMed, EMBASE, and the Cochrane, as well as journals and book reference lists. The review highlights the pathophysiological processes underpinning cancer development and the molecular actions of anesthetic agents, pre-clinical and retrospective studies investigating cancer and anesthetics, as well as ongoing clinical trials. Overall, there are conflicting results regarding the impact of regional vs. general anesthesia on cancer recurrence, whilst the majority of data suggest a benefit of the use of intravenous propofol over inhalational volatile anesthetics. The biological changes associated with the surgical inflammatory response offer a unique opportunity to intervene to counteract any potentially cancer-promoting effects.

Disease activity and its predictors in early inflammatory arthritis: findings from a national cohort.

OBJECTIVES: We set out to characterize patient factors that predict disease activity during the first year of treatment for early inflammatory arthritis (EIA). METHODS: We used an observational cohort study design, extracting data from a national clinical audit. All NHS organizations providing secondary rheumatology care in England and Wales were eligible to take part, with recruitment from 215/218 (99%) clinical commissioning groups (CCGs)/Health Boards. Participants were >16 years old and newly diagnosed with RA pattern EIA between May 2018 and May 2019. Demographic details collected at baseline included age, gender, ethnicity, work status and postcode, which was converted to an area level measure of socioeconomic position (SEP). Disease activity scores (DAS28) were collected at baseline, three and 12 months follow-up. RESULTS: A total of 7455 participants were included in analyses. Significant levels of CCG/Health board variation could not be robustly identified from mixed effects modelling. Gender and SEP were predictors of low disease activity at baseline, three and 12 months follow-up. Mapping of margins identified a gradient for SEP, whereby those with higher degrees of deprivation had higher disease activity. Black, Asian and Minority Ethnic patients had lower odds of remission at three months follow-up. CONCLUSION: Patient factors (gender, SEP, ethnicity) predict disease activity. The rheumatology community should galvanise to improve access to services for all members of society. More data are required to characterize area level variation in disease activity.

Venous Thromboembolism Risk With JAK Inhibitors: A Meta-Analysis.

OBJECTIVE: JAK inhibitor therapies are effective treatment options for immune-mediated inflammatory diseases (IMIDs), but their use has been limited by venous thromboembolism (VTE) risk warnings from licensing authorities. We undertook this study to evaluate the VTE risk of JAK inhibitors in patients with IMIDs. METHODS: Systematic searches of Medline and Embase databases from inception to September 30, 2020 were conducted. Phase II and phase III double-blind, randomized controlled trials (RCTs) of JAK inhibitors at licensed doses were included in our analyses. RCTs with no placebo arm, long-term extension studies, post hoc analyses, and pooled analyses were excluded. Three researchers independently extracted data on exposure to JAK inhibitors or placebo and VTE events (e.g., pulmonary embolism [PE] and deep vein thrombosis [DVT]) and assessed study quality. RESULTS: A total of 42 studies were included, from an initial search that yielded 619. There were 6,542 JAK inhibitor patient exposure years (PEYs) compared to 1,578 placebo PEYs. There were 15 VTE events in the JAK inhibitor group and 4 in the placebo group. The pooled incidence rate ratios (IRRs) of VTE, PE, and DVT in patients receiving JAK inhibitors were 0.68 (95% confidence interval [95% CI] 0.36-1.29), 0.44 (95% CI 0.28-0.70), and 0.59 (95% CI 0.31-1.15), respectively. CONCLUSION: This meta-analysis of RCT data defines the VTE risk with JAK inhibitors as a class in IMID patients. The pooled IRRs do not provide evidence that support the current warnings of VTE risk for JAK inhibitors. These findings will aid continued development of clinical guidelines for the use of JAK inhibitors in IMIDs.

Hepatic ischemia-reperfusion injury in liver transplant setting: mechanisms and protective strategies.

Hepatic ischemia-reperfusion injury is a major cause of liver transplant failure, and is of increasing significance due to increased use of expanded criteria livers for transplantation. This review summarizes the mechanisms and protective strategies for hepatic ischemia-reperfusion injury in the context of liver transplantation. Pharmacological therapies, the use of pre-and post-conditioning and machine perfusion are discussed as protective strategies. The use of machine perfusion offers significant potential in the reconditioning of liver grafts and the prevention of hepatic ischemia-reperfusion injury, and is an exciting and active area of research, which needs more study clinically.

Postoperative sleep disorders and their potential impacts on surgical outcomes.

Postoperative sleep disturbance is a common occurrence with significant adverse effects on patients including delayed recovery, impairment of cognitive function, pain sensitivity and cardiovascular events. The development of postoperative sleep disturbance is multifactorial and involves the surgical inflammatory response, the severity of surgical trauma, pain, anxiety, the use of anesthetics and environmental factors such as nocturnal noise and light levels. Many of these factors can be managed perioperatively to minimize the deleterious impact on sleep. Pharmacological and non-pharmacological treatment strategies for postoperative sleep disturbance include dexmedetomidine, zolpidem, melatonin, enhanced recovery after surgery (ERAS) protocol and controlling of environmental noise and light levels. It is likely that a combination of pharmacological and non-pharmacological therapies will have the greatest impact; however, further research is required before their use can be routinely recommended.

Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence.

BACKGROUND: Herpes simplex virus (HSV) has been implicated in the etiology of recurrent aphthous ulcers, cold sores, and genital sores. PRIMARY STUDY OBJECTIVE: To summarize the research evidence for use of L-lysine to prevent HSV disease recurrence, a use not widely recognized by doctors. METHODS/DESIGN: Two scientists conducted a literature search of EMBASE, Medline, AMED, and CINAHL for the expanded terms lysine and herpes simplex or HSV in the title field and then independently screened the abstracts for clinically relevant articles. Disagreements on article inclusion were discussed before the literature was reviewed to see whether lysine is effective for preventing herpes simplex relapse. INTERVENTION: Oral L-lysine supplements were taken daily. PRIMARY OUTCOME MEASURES: Described individually for each trial reviewed. RESULTS: L-lysine supplementation appears to be ineffective for prophylaxis or treatment of herpes simplex lesions with doses of less than 1 g/d without low-arginine diets. Doses in excess of 3 g/d appear to improve patients' subjective experience of the disease. CONCLUSION: Longer duration controlled studies of daily lysine doses exceeding 1.2 g/d are required to definitively test its role in herpes simplex prophylaxis. Patients with cardiovascular or gallbladder disease should be cautioned and warned of the theoretical risks of lysine supplementation.