Colorectal Cancer Screening and Perceived Disgust:The Importance of the Ick Factor in Faecal Occult Blood Test Uptake

Background: Colorectal cancer is a major cause of cancer deaths worldwide. Screening is key to early detection but uptake of national programmes is poor, especially amongst those from lower socio-economic backgrounds. Decisions not to take up screening may be based more on emotional rather than rational evaluations. We aimed to examine the importance of perceived disgust (the ‘ICK’ factor) in determining colorectal cancer screening uptake, in a large, randomised controlled trial. Methods: This paper reports secondary analysis of a randomised controlled trial of a simple, questionnaire-based Anticipated Regret (AR) intervention, which was delivered alongside existing pre-notification letters. 60,000 adults aged 50- 74 who were participant in the Scottish National Screening programme were randomised to one of 3 treatment arms: 1) no questionnaire (control), 2) Health Locus of Control (HLOC) questionnaire or 3) AR questionnaire. Primary outcome was Faecal Occult Blood Test kit return (FOBT uptake). 13,645 people completed questionnaires of secondary outcomes including intention to return test kit and a new self-report measure of perceived disgust (ICK-C). Results: Intentions, ICK and AR were all predictors of FOBT uptake; however, for people who expressed strong intentions to return their FOBT kit, only ICK differentiated kit returners from non-returners, with non-returners reporting higher disgust (mean difference=0.51; 95% CI for difference (0.37, 0.64), Cohen’s d=0.34). The 4-item ICK-C showed excellent internal reliability and predictive validity with regard to an objective measure i.e., FOBT uptake. Conclusions: The findings show that perceived disgust is an important emotional psychological construct in determining uptake of colorectal cancer screening. We also demonstrated that a simple 4-item scale (the ‘ICK-C), developed to be used in research on colorectal cancer screening, has excellent psychometric properties

Is an opportunistic primary care-based intervention for non-responders to bowel screening feasible and acceptable?:A mixed-methods feasibility study in Scotland

Objectives We aimed to test whether a brief, opportunistic intervention in general practice was a feasible and acceptable way to engage with bowel screening non-responders. Design This was a feasibility study testing an intervention which comprised a brief conversation during routine consultation, provision of a patient leaflet and instructions to request a replacement faecal occult blood test kit. A mixed-methods approach to evaluation was adopted. Data were collected from proformas completed after each intervention, from the Bowel Screening Centre database and from questionnaires. Semi-structured interviews were carried out. We used descriptive statistics, content and framework analysis to determine intervention feasibility and acceptability. Participants Bowel screening non-responders (as defined by the Scottish Bowel Screening Centre) and primary care professionals working in five general practices in Lothian, Scotland. Primary and secondary outcome measures Several predefined feasibility parameters were assessed, including numbers of patients engaging in conversation, requesting a replacement kit and returning it, and willingness of primary care professionals to deliver the intervention. Results The intervention was offered to 258 patients in five general practices: 220 (87.0%) engaged with the intervention, 60 (23.3%) requested a new kit, 22 (8.5%) kits were completed and returned. Interviews and questionnaires suggest that the intervention was feasible, acceptable and consistent with an existing health prevention agenda. Reported challenges referred to work-related pressures, time constraints and practice priorities. Conclusions This intervention was acceptable and resulted in a modest increase in non-responders participating in bowel screening, although outlined challenges may affect sustained implementation. The strategy is also aligned with the increasing role of primary care in promoting bowel screening

Anticipated regret to increase uptake of colorectal cancer screening (ARTICS):a randomised controlled trial

Objective. Screening is key to early detection of colorectal cancer. Our aim was to determine whether a simple anticipated regret (AR) intervention could increase colorectal cancer screening uptake. Methods. We conducted a randomised controlled trial of a simple, questionnaire-based AR intervention, delivered alongside existing pre-notification letters. 60,000 adults aged 50-74 from the Scottish National Screening programme were randomised to: 1) no questionnaire (control), 2) Health Locus of Control questionnaire (HLOC) or 3) HLOC plus anticipated regret questionnaire (AR). Primary outcome was guaiac Faecal Occult Blood Test (FOBT) return. Secondary outcomes included intention to return test kit and perceived disgust (ICK). Results. 59,366 people were analysed as allocated (Intentionto- treat (ITT)); there were no overall differences between treatment groups on FOBT uptake (control: 57.3%, HLOC: 56.9%, AR: 57.4%). 13,645 (34.2%) people returned questionnaires. Analysis of the secondary questionnaire measures showed that AR had an indirect effect on FOBT uptake via intention, whilst ICK had a direct effect on FOBT uptake over and above intention. The effect of AR on FOBT uptake was also moderated by intention strength: for less than strong intenders only, uptake was 4.2% higher in the AR (84.6%) versus the HLOC group (80.4%) (95% CI for difference (2.0, 6.5)). Conclusion. The findings show that psychological concepts including anticipated regret and perceived disgust (ICK) are important factors in determining FOBT uptake. However, there was no simple effect of the AR intervention in the ITT. We conclude that exposure to AR in those with low intentions may be required to increase FOBT uptake. Current controlled trials: www.controlledtrials. com number: ISRCTN74986452

Anticipated regret to increase uptake of colorectal cancer screening in Scotland (ARTICS): Study protocol for a randomised controlled trial

Background: Colorectal cancer is the second leading cause of cancer deaths in the UK. Screening is key to early detection. The Scottish programme of colorectal cancer screening is running successfully, and involves all adults aged between 50 and 74 years being invited to post back a faecal sample for testing every 2 years. However, screening uptake is sub-optimal: for example rates for the period November 2009 to October 2011 ranged from just 39% for males living in the most deprived areas to 67% for least deprived females. Recent research has shown that asking people to consider the emotional consequences of not participating in screening (anticipated regret) can lead to a significant increase in screening uptake. Methods/Design: We will test a simple anticipated regret manipulation, in a large randomised controlled trial with 60,000 members of the general public. They will be randomly allocated to one of 3 arms, no questionnaire, control questionnaire or anticipated regret questionnaire. The primary outcome will be screening test kit return. Results will also be examined by demographic variables (age, gender, deprivation) as these are currently related to screening kit return. Discussion: If this anticipated regret intervention leads to a significant increase in colorectal cancer screening kit returns, this would represent a rare example of a theoretically-driven, simple intervention that could result in earlier detection of colorectal cancer and many more lives saved. Trial registration: Current Controlled trials: ISRCTN7498645

Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes

Objective To determine the role of markers of plasma protein damage by glycation, oxidation and nitration in microalbuminuria onset or subsequent decline of glomerular filtration rate (termed “early GFR decline”) in patients with type 1 diabetes. Methods From the 1st Joslin Kidney Study, we selected 30 patients with longstanding normoalbuminuria and 55 patients with new onset microalbuminuria. Patients with microalbuminuria had 8–12 years follow-up during which 33 had stable GFR and 22 early GFR decline. Mean baseline GFRCYSTATIN C was similar between the three groups. Glycation, oxidation and nitration markers were measured in protein and ultrafiltrate at baseline by liquid chromatography-tandem mass spectrometry using the most reliable methods currently available. Results Though none were significantly different between patients with microalbuminuria with stable or early GFR decline, levels of 6 protein damage adduct residues of plasma protein and 4 related free adducts of plasma ultrafiltrate were significantly different in patients with microalbuminuria compared to normoalbuminuria controls. Three protein damage adduct residues were decreased and 3 increased in microalbuminuria while 3 free adducts were decreased and one increased in microalbuminuria. The most profound differences were of N-formylkynurenine (NFK) protein adduct residue and Nω-carboxymethylarginine (CMA) free adduct in which levels were markedly lower in microalbuminuria (P<0.001 for both). Conclusions Complex processes influence levels of plasma protein damage and related proteolysis product free adducts in type 1 diabetes and microalbuminuria. The effects observed point to the possibility that patients who have efficient mechanisms of disposal of damaged proteins might be at an increased risk of developing microalbuminuria but not early renal function decline. The findings support the concept that the mechanisms responsible for microalbuminuria may differ from the mechanisms involved in the initiation of early renal function decline

Why we need easy access to all data from all clinical trials and how to accomplish it

International calls for registering all trials involving humans and for sharing the results, and sometimes also the raw data and the trial protocols, have increased in recent years. Such calls have come, for example, from the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO), the US National Institutes of Heath, the US Congress, the European Commission, the European ombudsman, journal editors, The Cochrane Collaboration, and several funders, for example the UK Medical Research Council, the Wellcome Trust, the Bill and Melinda Gates Foundation and the Hewlett Foundation

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication