A validated severity score for haemorrhoids as an essential prerequisite for future haemorrhoid trials.

BACKGROUND: There is a lack of standardised outcomes for haemorrhoidal disease making comparison between trials difficult. A need for a very well validated severity score is essential to facilitate meta-analysis of comparative studies, enabling evidence-based clinical practice. METHODS: The Hubble trial provides a large cohort of patients with haemorrhoidal disease randomised to rubber band ligation (RBL) or haemorrhoidal artery ligation. The haemorrhoid severity score (HSS) was collected on each patient at baseline, 6 weeks and 1 year after intervention. This allows for the responsiveness of the HSS instrument to be examined and compared with a more specific instrument, the Vaizey incontinence score (also collected). Responsiveness was tested using four methods (effect size, standardised response means (SRM), significance of change, and responsiveness statistic). RESULTS: The four tests of responsiveness demonstrated that the HSS was more responsive to changes in the patient's health status following both of the interventions compared to the Vaizey questionnaire. For example, between baseline and 6 weeks, the RBL intervention effect size scores and SRM calculations indicated a non-significant small amount of change (0.20 and 0.16 respectively). However, using the HSS, the effect size and SRM demonstrated a large magnitude of change (1.12 and 1.01, respectively) which was significant. Similar results were observed at 1 year. Significance of change scores and the index of responsiveness were also higher for the HSS questionnaire than the Vaizey across both treatment modalities. CONCLUSIONS: The HSS is a highly responsive tool for the detection of changes in haemorrhoid symptoms. It should form an essential patient-reported outcome tool for future studies on haemorrhoidal disease

Emergency general surgery: impact of distance and rurality on mortality

Funding This work was made possible by a grant from NHS Grampian and NHS Highlands Endowment Funding. No funding was received from the National Institutes of Health (NIH); Wellcome Trust; or Howard Hughes Medical Institute (HHMI). Acknowledgements The authors acknowledge the support of the eDRIS Team (Public Health Scotland) for their involvement in obtaining approvals, provisioning, and linking data, and the use of the secure analytical platform within the National Safe Haven. We also acknowledge P. Murchie for support with contextualizing the work within the rural medical practitioner literature.Peer reviewedPublisher PD

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi—a process termed ‘cell shedding’. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes

A physical activity intervention to improve the quality of life of patients with a stoma: a feasibility study protocol.

Background:Physical activity (PA) is positively associated with quality of life. People with a stoma are less likely to engage in PA than those without a stoma. Methods:In this feasibility intervention study, we will perform the following: (1) Develop a PA intervention for people with a stoma. An Expert Working Group of behavioural scientists, exercise scientists, clinicians and a Patient Advisory Group of people with a bowel stoma will meet with the research team to inform the development of a PA intervention for people with a stoma. A manual of the intervention will be the main output. (2) Explore PA instructors' experiences of delivering the PA intervention. PA instructors will record on paper the number of PA consultations with each patient and a researcher will interview the PA instructors about their experiences of delivering the intervention. (3) Assess the level of patient (bowel cancer or inflammatory bowel disease (IBD) patients with a stoma between 6 weeks and 24 months post-surgery) engagement with the PA intervention and their views on intervention acceptability and usefulness. Patients will keep a PA diary to record daily pedometer recorded step count and type and duration of activities. A researcher will interview patients about their experiences of the PA intervention. (4) Assess screening, eligibility, consent, data completion, loss to follow up, and missing data rates, representativeness of participants and potential treatment effects. A researcher will record on paper all study procedure parameters. Quality of life (stoma-quality of life; Functional Assessment of Cancer Therapy, Short IBD questionnaire), fatigue (FACIT fatigue scale) and PA (accelerometer) will be measured pre- and post-intervention in patients. For IBD patients only, blood will be taken to measure systemic inflammation. Discussion:We hypothesise that a PA intervention will be an effective means of improving the quality of life of people with a stoma. Before embarking on a full randomised controlled trial to test this hypothesis, a PA intervention needs to be developed and a feasibility study of the proposed PA intervention conducted. Trial registration:ISRCTN58613962, Protocol version: 0.1. 14 September 2017

“Girls Aren’t Meant to Exercise”: Perceived Influences on Physical Activity among Adolescent Girls—The HERizon Project

Background. Adolescent girls are less active than boys, with approximately 10% of girls in Ireland and the United Kingdom meeting the minimum recommended daily physical activity (PA) guidelines. This study investigated factors perceived to influence PA among adolescent girls from low socioeconomic areas in order to inform the design of a future intervention (The HERizon Project). Methods. A total of 48 adolescent girls (13–18 years) from low socioeconomic areas of the United Kingdom and Ireland participated in focus groups (n = 8), to explore perspectives of physical activity and the influence of gender within this. Focus groups were thematically analyzed and interpreted within a socioecological framework. Results. Most girls enjoyed PA and were aware of its benefits. They identified both barriers and facilitators to PA at intrapersonal (fear of judgement and changing priorities WITH age), interpersonal (changing social pressures and support from others) and organizational (delivery of PE) levels. Gender inequality was a multilevel factor, crossing all socioecological levels. Conclusion. Although many adolescent girls enjoy PA, their experiences appear to be limited by a fear of judgement and an overarching sense of gender inequality. Future interventions, such as the HERizon Project, should address influences at intrapersonal, interpersonal and organizational levels to promote positive PA experiences for adolescent girls

Cost effectiveness of stapled haemorrhoidopexy and traditional excisional surgery for the treatment of haemorrhoidal disease

Objective Our objective was to compare the cost effectiveness of stapled haemorrhoidopexy (SH) and traditional haemorrhoidectomy (TH) in the treatment of grade II–IV haemorrhoidal disease from the perspective of the UK national health service. Methods An economic evaluation was conducted alongside an open, two-arm, parallel-group, pragmatic, multicentre, randomised controlled trial conducted in several hospitals in the UK. Patients were randomised into either SH or TH surgery between January 2011 and August 2014 and were followed up for 24 months. Intervention and subsequent resource use data were collected using case review forms and questionnaires. Benefits were collected using the EQ-5D-3L (EuroQoL—five dimensions—three levels) instrument. The primary economic outcome was incremental cost measured in pounds (£), year 2016 values, relative to the incremental benefit, which was estimated using quality-adjusted life-years (QALYs). Cost and benefits accrued in the second year were discounted at 3.5%. The base-case analysis was based on imputed data. Uncertainty was explored using univariate sensitivity analyses. Results Participants (n = 777) were randomised to SH (n = 389) or TH (n = 388). The mean cost of SH was £337 (95% confidence interval [CI] 251–423) higher than that of TH and the mean QALYs were −0.070 (95% CI −0.127 to −0.011) lower than for TH. The base-case cost-utility analysis indicated that SH has zero probability of being cost effective at both the £20,000 and the £30,000 threshold. Results from the sensitivity analyses were similar to those from the base-case analysis. Conclusions The evidence suggests that, on average, the total mean costs over the 24-month follow-up period were significantly higher for the SH arm than for the TH arm. The QALYs were also, on average, significantly lower for the SH arm. These results were supported by the sensitivity analyses. Therefore, in terms of cost effectiveness, TH is a superior surgical treatment for the management of grade II–IV haemorrhoids when compared with SH

Cost-Effectiveness of Haemorrhoidal Artery Ligation versus Rubber Band Ligation for the Treatment of Grade II–III Haemorrhoids: Analysis Using Evidence from the HubBLe Trial

Aim Haemorrhoids are a common condition, with nearly 30,000 procedures carried out in England in 2014/15, and result in a significant quality-of-life burden to patients and a financial burden to the healthcare system. This study examined the cost effectiveness of haemorrhoidal artery ligation (HAL) compared with rubber band ligation (RBL) in the treatment of grade II–III haemorrhoids. Method This analyses used data from the HubBLe study, a multicentre, open-label, parallel group, randomised controlled trial conducted in 17 acute UK hospitals between September 2012 and August 2015. A full economic evaluation, including long-term cost effectiveness, was conducted from the UK National Health Service (NHS) perspective. Main outcomes included healthcare costs, quality-adjusted life-years (QALYs) and recurrence. Costeffectiveness results were presented in terms of incremental cost per QALY gained and cost per recurrence avoided. Extrapolation analysis for 3 years beyond the trial follow-up, two subgroup analyses (by grade of haemorrhoids and recurrence following RBL at baseline), and various sensitivity analyses were undertaken. Results In the primary base-case within-trial analysis, the incremental total mean cost per patient for HAL compared with RBL was £1027 (95% confidence interval [CI] £782– £1272, p\0.001). The incremental QALYs were 0.01 QALYs (95% CI -0.02 to 0.04, p = 0.49). This generated an incremental cost-effectiveness ratio (ICER) of £104,427 per QALY. In the extrapolation analysis, the estimated probabilistic ICER was £21,798 per QALY. Results from all subgroup and sensitivity analyses did not materially change the base-case result. Conclusions Under all assessed scenarios, the HAL procedure was not cost effective compared with RBL for the treatment of grade II-III haemorrhoids at a cost-effectiveness threshold of £20,000 per QALY; therefore

Formative Evaluation of a Home-Based Physical Activity Intervention for Adolescent Girls-The HERizon Project: A Randomised Controlled Trial.

BACKGROUND: This is a formative evaluation study of the HERizon Project, a home-based multi-component physical activity (PA) intervention for adolescent girls in the UK and Ireland. Although not intended, this study coincided with the initial COVID-19 lockdown restrictions. METHODS: A total of 42 female participants, aged 13 to 16 years old (mean = 14.2, SD = 1.1), were randomly allocated to: (i) the HERizon group (n = 22) or (ii) the wait-list control group (n = 20). Participants in the six-week HERizon group were asked to complete three PA sessions each week and engage in weekly behaviour change support video calls. The primary outcome measure was self-reported habitual PA. Secondary outcomes measures included cardiorespiratory fitness (20 m shuttle run), muscular strength (standing long jump), muscular endurance (push up test), and psychosocial outcomes (Perceived Competence Scale, Body Appreciation Scale, Self-Esteem Questionnaire, Behavioural Regulation in Exercise Questionnaire). Quantitative and qualitative process evaluation data were also collected. Outcome measures were assessed at baseline and after the six-week intervention. RESULTS: There was no significant change in habitual PA between groups (LMM group*time interaction: p = 0.767). The HERizon group had significantly increased cardiorespiratory fitness (p = 0.001), muscular endurance (p = 0.022), intrinsic motivation (p = 0.037), and body appreciation (p < 0.003) in comparison to the wait-list control group. All participants in the intervention group completed the intervention and compliance to the intervention was high (participants completed 18 ± 2 sessions). CONCLUSIONS: Although no change in PA was observed, HERizon resulted in improved physical fitness and psychosocial outcomes. These preliminary findings, alongside positive findings for feasibility and acceptability, highlight potential benefits from the home-based intervention, thus further investigation is warranted

An Arthropod Enzyme, Dfurin 1, and a Vertebrate Furin Homolog Display Distinct Cleavage Site Sequence Preferences for a Shared Viral Proprotein Substrate

Alphaviruses replicate in vertebrate and arthropod cells and utilize a cellular enzyme called furin to process the PE2 glycoprotein precursor during virus replication in both cell types. Furin cleaves PE2 at a site immediately following a highly conserved four residue cleavage signal. Prior studies demonstrated that the amino acid immediately adjacent to the cleavage site influenced PE2 cleavage differently in vertebrate and mosquito cells (HW Heidner et al. 1996. Journal of Virology 70: 2069–2073.). This finding was tentatively attributed to potential differences in the substrate specificities of the vertebrate and arthropod furin enzymes or to differences in the carbohydrate processing phenotypes of arthropod and vertebrate cells. To further address this issue, we evaluated Sindbis virus replication and PE2 cleavage in the Chinese hamster, Cricetulus griseus Milne-Edwards (Rodentia: Cricetidae) ovary cells (CHO-K1) and in a CHO-K1-derived furin-negative cell line (RPE.40) engineered to stably express the Dfurin1 enzyme of Drosophila melanogaster Meigen (Diptera: Drosophilidae). Expression of Dfurin1 enhanced Sindbis virus titers in RPE.40 cells by a factor of 102 – 103, and this increase correlated with efficient cleavage of PE2. The PE2-cleavage phenotypes of viruses containing different amino acid substitutions adjacent to the furin cleavage site were compared in mosquito (C6/36), CHO-K1, and Dfurin1-expressing RPE.40 cells. This analysis confirmed that the substrate specificities of Dfurin1 and the putative mosquito furin homolog present in C6/36 cells are similar and suggested that the alternative PE2 cleavage phenotypes observed in vertebrate and arthropod cells were due to differences in substrate specificity between the arthropod and vertebrate furin enzymes and not to differences in host cell glycoprotein processing pathways