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

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

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

Combined changes in Wnt signalling response and contact inhibition induce altered proliferation in radiation treated intestinal crypts

Curative intervention is possible if colorectal cancer is identified early, underscoring the need to detect the earliest stages of malignant transformation. A candidate biomarker is the expanded proliferative zone observed in crypts before adenoma formation, also found in irradiated crypts. However, the underlying driving mechanism for this is not known. Wnt signaling is a key regulator of proliferation, and elevated Wnt signaling is implicated in cancer. Nonetheless, how cells differentiate Wnt signals of varying strengths is not understood. We use computational modeling to compare alternative hypotheses about how Wnt signaling and contact inhibition affect proliferation. Direct comparison of simulations with published experimental data revealed that the model that best reproduces proliferation patterns in normal crypts stipulates that proliferative fate and cell cycle duration are set by the Wnt stimulus experienced at birth. The model also showed that the broadened proliferation zone induced by tumorigenic radiation can be attributed to cells responding to lower Wnt concentrations and dividing at smaller volumes. Application of the model to data from irradiated crypts after an extended recovery period permitted deductions about the extent of the initial insult. Application of computational modeling to experimental data revealed how mechanisms that control cell dynamics are altered at the earliest stages of carcinogenesis

“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

Remote physical activity intervention to promote physical activity and health in adolescent girls (the HERizon project): a multi-arm, pilot randomised trial

Background Engaging in physical activity (PA) during adolescence is beneficial for health and positive development. However, most adolescent girls have low PA levels, and there is a need for interventions outside of school hours. This pilot randomised controlled trial aimed to explore the preliminary effectiveness of three different remote PA interventions in increasing adolescent girls’ moderate-to- vigorous PA (MVPA), fitness and psychosocial outcomes. Methods Girls living in the UK or Ireland, aged between 13 and 16 years old, who wished to increase their activity levels, were eligible for the study. Using a random number generator, participants (n = 153; 14.8y ± 1.4) were randomised into one of three 12-week intervention groups (i) PA programme, (ii) Behaviour change support, or (iii) Combined PA programme and Behaviour change support, or (iv) a Comparison group. Outcome measures included accelerometer and self-reported PA, physical fitness (cardiorespiratory fitness; 20 m shuttle run, muscular endurance; push up, muscular strength; long jump), and psychosocial assessments (perceived competence; body appreciation; self-esteem; behavioural regulation). Linear mixed models were used to analyse differences between each intervention arm and the comparison group immediately postintervention (12 weeks) and at follow up (3-months post-intervention), while adjusting for potential confounders. Results Participation in the PA programme group was associated with higher perceived competence (0.6, 95% CI 0.1 to 1.2), identified regulation (0.7, 95% CI 0.2 to 1.1) and intrinsic motivation (0.9, 95% CI 0.2 to 1.6) at post-intervention. Participation in the Behaviour change group was associated with higher perceived competence at post-intervention (0.6, 95% CI 0.1 to 1.2), and higher push-up scores at the 3-month follow-up (4.0, 95% CI 0.0 to 7.0). Participation in the Combined group was also associated with higher perceived competence at post-intervention (0.8, 95% CI 0.2 to 1.4), and higher push-up scores at the 3-month follow-up (5.0, 95% CI 1.0 to 8.0). No other significant differences were found between the intervention arms and the comparison group. Conclusion Results suggest perceived competence increased across all intervention arms, while the PA programme group enhanced autonomous motivation in the short term. Intervention arms with behaviour change support appear most promising in improving muscular endurance. However, a larger scale trial is needed for a better understanding of between-group differences and the impact of intervention arms on MVPA and fitness, given the small sample size and short-term follow-up