Background: Rehabilitation potential involves predicting who will benefit from rehabilitation. Decisions about rehabilitation potential must take into account personal, clinical and contextual factors, a process which is complicated in the presence of acute ill-health and frailty. This study aimed to evaluate the feasibility and acceptability of the Rehabilitation Potential Assessment Tool (RePAT) - a 15 item holistic, person-centred assessment tool and training package - in the acute hospital setting. Method(s): A non-randomised feasibility study with nested semi-structured interviews explored whether RePAT was feasible and acceptable. Feasibility was tested by recruiting physiotherapy and occupational therapy participants delivering the RePAT intervention to patients alongside usual clinical care. Acceptability was tested by conducting semi-structured interviews with staff, patient and carer participants. Staff and patient characteristics were analysed using descriptive statistics. Interview data were analysed thematically. Fidelity of completed RePAT items was assessed against a priori criteria on how closely they matched tool guidance by two researchers. Mean values of the two scores were calculated. RePAT content was analysed and supported with verbatim quotes. Result(s): Six staff participants were recruited and trained. They assessed 26 patient participants using RePAT. Mean (SD) patient age was 86.16 (+/-6.39) years. 32% were vulnerable or mildly frail, 42% moderately frail and 26% severely or very severely frail using the Clinical Frailty Scale. Mean (SD) time to complete RePAT was 32.7 (+/-9.6) minutes. RePAT fidelity was good where 13 out of 15 items achieved a priori fidelity. RePAT was acceptable and tolerated by staff and patients. Staff participants reported RePAT enabled them to consider rehabilitation decisions in a more structured and consistent way. Patients and carer participants, although unable to comment directly on RePAT, reported being satisfied with their rehabilitation assessments which were found to embrace a person-centred approach. Conclusion(s): RePAT was found to be acceptable and feasible by staff, carers and patients. It allowed clinicians to make explicit their reasoning behind rehabilitation assessments and encouraged them to become more cognisant of factors which affected their clinical decision-making. Trial registration: ID ISRCTN31938453. Registered 05/10/2021. Copyright © 2022, The Author(s).

Senior research nurse and RCN Gastroenterology Committee team member, Amanda Cetroni, highlights the diverse skills required for her role and emphasises the importance of clinical research for improving healthcare outcomes.

Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including beta-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts in vitro. Therapeutic effects have been seen in animal models in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from in vitro, in vivo and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections. Copyright: © 2021 Bath PM et al.

Despite high survival rates of children and young people diagnosed with a brain tumour, survival is often associated with poor psychological, physical, and social outcomes. Acceptance and Commitment Therapy (ACT) is an evidence-based psychological intervention shown to improve psychological and physical outcomes in adults and children with chronic disease, including cancer. The ACT Now study investigates the feasibility of ACT delivered remotely with young people who have experienced a brain tumour. This study aims to describe participant experience whilst better understanding the impact of therapy and capturing the barriers and facilitators to engagement. Participants of the ACT Now study were invited to take part in a semi-structured interview with questions covering experience of study initiation, receipt of ACT, remote delivery and overall impact of ACT. Ten participants who had previously undergone treatment for a brain tumour have been interviewed to date. Interviews were transcribed verbatim and coded into broad themes. We found that pre-therapy mood and altruism served as motivation for interviewees' involvement in the study. Interviewees reported hoping to learn coping techniques to navigate fluctuating moods and the pressures of young adult life. Despite the technology used for remote delivery occasionally malfunctioning, interviewees reported increased ability to access therapy via this method. However, an overall preference for face-to-face therapy delivery was reported with interviewees describing that they felt communication might have been easier in person. The therapeutic relationship and the therapists' flexible schedules were seen as facilitators to session attendance. Barriers to attendance were scarcely reported but included scheduling conflicts due to work or school. ACT was highly regarded amongst interviewees and provided an opportunity for them to learn about themselves and how they can live in accordance with their personal values. Interviewees benefitted from ACT psychologically, physically, and socially and reported an overall positive experience of study involvement.

Abstract Background Specialized proresolution molecules (SPMs) halt the transition to chronic pathogenic inflammation. We aimed to quantify serum levels of pro- and anti-inflammatory bioactive lipids in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, and to identify potential relationships with innate responses and clinical outcome. Methods Serum from 50 hospital admitted inpatients (22 female, 28 male) with confirmed symptomatic SARS-CoV-2 infection and 94 age- and sex-matched controls collected prior to the pandemic (SARS-CoV-2 negative), were processed for quantification of bioactive lipids and anti-nucleocapsid and anti-spike quantitative binding assays. Results SARS-CoV-2 serum had significantly higher concentrations of omega-6–derived proinflammatory lipids and omega-6– and omega-3–derived SPMs, compared to the age- and sex-matched SARS-CoV-2–negative group, which were not markedly altered by age or sex. There were significant positive correlations between SPMs, proinflammatory bioactive lipids, and anti-spike antibody binding. Levels of some SPMs were significantly higher in patients with an anti-spike antibody value >0.5. Levels of linoleic acid and 5,6-dihydroxy-8Z,11Z,14Z-eicosatrienoic acid were significantly lower in SARS-CoV-2 patients who died. Conclusions SARS-CoV-2 infection was associated with increased levels of SPMs and other pro- and anti-inflammatory bioactive lipids, supporting the future investigation of the underlying enzymatic pathways, which may inform the development of novel treatments.

INTRODUCTION: Professional footballers commonly experience sports-related injury and repetitive microtrauma to the foot and ankle, placing them at risk of subsequent chronic pain and osteoarthritis (OA) of the foot and ankle. Similarly, repeated heading of the ball, head/neck injuries and concussion have been implicated in later development of neurodegenerative diseases such as dementia. A recent retrospective study found that death from neurodegenerative diseases was higher among former professional soccer players compared with age matched controls. However, well-designed lifetime studies are still needed to provide evidence regarding the prevalence of these conditions and their associated risk factors in retired professional football players compared with the general male population. OBJECTIVES: To determine whether former professional male footballers have a higher prevalence than the general male population of: (1) foot/ankle pain and radiographic OA; and (2) cognitive and motor impairments associated with dementia and Parkinson's disease. Secondary objectives are to identify specific football-related risk factors such as head impact/concussion for neurodegenerative conditions and foot/ankle injuries for chronic foot/ankle pain and OA. METHODS AND ANALYSIS: This is a cross-sectional, comparative study involving a questionnaire survey with subsamples of responders being assessed for cognitive function by telephone assessment, and foot/ankle OA by radiographic examination. A sample of 900 adult, male, ex professional footballers will be recruited and compared with a control group of 1100 age-matched general population men between 40 and 100 years old. Prevalence will be estimated per group. Poisson regression will be performed to determine prevalence ratio between the populations and logistic regression will be used to examine risk factors associated with each condition in footballers. ETHICS AND DISSEMINATION: This study was approved by the East Midlands-Leicester Central Research Ethics Committee on 23 January 2020 (REC ref: 19/EM/0354). The study results will be disseminated at national and international meetings and submitted for peer-review publication. Copyright © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 x 10-5). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 x 10-6). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion(s): This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.Copyright © 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.

OBJECTIVE: To explore whether using a single matched or composite outcome might affect the results of previous randomized controlled trials (RCTs) testing exercise for non-specific low back pain (NSLBP). The first objective was to explore whether a single matched outcome generated greater standardized mean differences (SMDs) when compared with the original unmatched primary outcome SMD. The second objective was to explore whether a composite measure, composed of matched outcomes, generated a greater SMD when compared with the original primary outcome SMD. DESIGN: We conducted exploratory secondary analyses of data. SETTING: Seven RCTs were included, of which 2 were based in the USA (University research clinic, Veterans Affairs medical center) and the UK (primary care clinics, nonmedical centers). One each were based in Norway (clinics), Brazil (primary care), and Japan (outpatient clinics). PARTICIPANTS: The first analysis comprised 1) 5 RCTs (n=1033) that used an unmatched primary outcome but included (some) matched outcomes as secondary outcomes, and the second analysis comprised 2) 4 RCTs (n=864) that included multiple matched outcomes by developing composite outcomes (N=1897). INTERVENTION: Exercise compared with no exercise. MAIN OUTCOME MEASURES: The composite consisted of standardized averaged matched outcomes. All analyses replicated the RCTs' primary outcome analyses. RESULTS: Of 5 RCTs, 3 had greater SMDs with matched outcomes (pooled effect SMD 0.30 [95% confidence interval {CI} 0.04, 0.56], P=.02) compared with an unmatched primary outcome (pooled effect SMD 0.19 [95% CI -0.03, 0.40] P=.09). Of 4 composite outcome analyses, 3 RCTs had greater SMDs in the composite outcome (pooled effect SMD 0.28 [95% CI 0.05, 0.51] P=.02) compared with the primary outcome (pooled effect SMD 0.24 [95% CI -0.04, 0.53] P=.10). CONCLUSIONS: These exploratory analyses suggest that using an outcome matched to exercise treatment targets in NSLBP RCTs may produce greater SMDs than an unmatched primary outcome. Composite outcomes could offer a meaningful way of investigating superiority of exercise than single domain outcomes. Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.