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Background: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. Design: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (e.g., severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The two independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the two co-primary outcomes. Summary: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery. Population Health Research Institute

Objective The aim of this study was to investigate whether the use of off-pump coronary artery bypass (OPCAB) may enhance early outcomes in subjects with peripheral artery disease (PAD) undergoing coronary artery bypass grafting (CABG). Methods We employed a propensity-score (PS) method to compare early postoperative results of OPCAB and on-pump CABG patients with associated PAD. The study population consisted of 1,961 patients: 284 in the OPCAB and 1,677 in the on-pump CABG group. The inverse probability of treatment weighting was used as PS method. Results The incidence of death (1.2% [95% confidence interval, CI: –0.9 to 3.3%], p = 0.262), stroke (2.2% [95% CI: –1.4 to 5.7%], p = 0.235), acute kidney disease (1.5% [95% CI: –3.8 to 6.8%], p = 0.586), limb ischemia (3.2% [95% CI: –0.6 to 7.0%], p = 0.315), and low output syndrome (1.2% [95% CI: –0.9 to 3.3%], p = 0.262) did not differ between the two groups. On the other hand, the rate of cardiac death (1.2% [95% CI: –0.1 to 2.3%], p = 0.038) was significantly higher in on-pump CABG group. Conclusions The OPCAB procedure considerably reduced the occurrence of cardiac death after coronary revascularization. This finding might suggest that the OPCAB procedure should be considered as the first option in patients with higher cardiovascular risk scores. Further research is warranted.

The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services.Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance.74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively.Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs.ISRCTN18040196; Results.

Background In the UK, patients with one or two adenomas, of which at least one is ≥ 10 mm in size, or three or four small adenomas, are deemed to be at intermediate risk of colorectal cancer (CRC) and referred for surveillance colonoscopy 3 years post polypectomy. However, colonoscopy is costly, can cause discomfort and carries a small risk of complications. Objectives To determine whether or not annual faecal immunochemical tests (FITs) are effective, acceptable and cost saving compared with colonoscopy surveillance for detecting CRC and advanced adenomas (AAs). Design Diagnostic accuracy study with health psychology assessment and economic evaluation. Setting Participants were recruited from 30 January 2012 to 30 December 2013 within the Bowel Cancer Screening Programme in England. Participants Men and women, aged 60–72 years, deemed to be at intermediate risk of CRC following adenoma removal after a positive guaiac faecal occult blood test were invited to participate. Invitees who consented and returned an analysable FIT were included. Intervention We offered participants quantitative FITs at 1, 2 and 3 years post polypectomy. Participants testing positive with any FIT were referred for colonoscopy and not offered further FITs. Participants testing negative were offered colonoscopy at 3 years post polypectomy. Acceptibility of FIT was assessed using discussion groups, questionnaires and interviews. Main outcome measures The primary outcome was 3-year sensitivity of an annual FIT versus colonoscopy at 3 years for detecting advanced colorectal neoplasia (ACN) (CRC and/or AA). Secondary outcomes included participants’ surveillance preferences, and the incremental costs and cost-effectiveness of FIT versus colonoscopy surveillance. Results Of 8008 invitees, 5946 (74.3%) consented and returned a round 1 FIT. FIT uptake in rounds 2 and 3 was 97.2% and 96.9%, respectively. With a threshold of 40 µg of haemoglobin (Hb)/g faeces (hereafter referred to as µg/g), positivity was 5.8% in round 1, declining to 4.1% in round 3. Over three rounds, 69.2% (18/26) of participants with CRC, 34.3% (152/443) with AAs and 35.6% (165/463) with ACN tested positive at 40 µg/g. Sensitivity for CRC and AAs increased, whereas specificity decreased, with lower thresholds and multiple rounds. At 40 µg/g, sensitivity and specificity of the first FIT for CRC were 30.8% and 93.9%, respectively. The programme sensitivity and specificity of three rounds at 10 µg/g were 84.6% and 70.8%, respectively. Participants’ preferred surveillance strategy was 3-yearly colonoscopy plus annual FITs (57.9%), followed by annual FITs with colonoscopy in positive cases (31.5%). FIT with colonoscopy in positive cases was cheaper than 3-yearly colonoscopy (£2,633,382), varying from £485,236 (40 µg/g) to £956,602 (10 µg/g). Over 3 years, FIT surveillance could miss 291 AAs and eight CRCs using a threshold of 40 µg/g, or 189 AAs and four CRCs using a threshold of 10 µg/g. Conclusions Annual low-threshold FIT with colonoscopy in positive cases achieved high sensitivity for CRC and would be cost saving compared with 3-yearly colonoscopy. However, at higher thresholds, this strategy could miss 15–30% of CRCs and 40–70% of AAs. Most participants preferred annual FITs plus 3-yearly colonoscopy. Further research is needed to define a clear role for FITs in surveillance. Future work Evaluate the impact of ACN missed by FITs on quality-adjusted life-years. Trial registration Current Controlled Trials ISRCTN18040196. Funding National Institute for Health Research (NIHR) Health Technology Assessment programme, NIHR Imperial Biomedical Research Centre and the Bobby Moore Fund for Cancer Research UK. MAST Group Ltd provided FIT kits.

Background: The NHS Bowel Cancer Screening Programme in England offers biennial guaiac faecal occult blood testing (gFOBt). There is a socioeconomic gradient in participation and socioeconomically disadvantaged groups have worse colorectal cancer survival than more advantaged groups. We compared the effectiveness and cost of an enhanced reminder letter with the usual reminder letter on overall uptake of gFOBt and the socioeconomic gradient in uptake. Methods: We enhanced the usual reminder by including a heading ‘A reminder to you’ and a short paragraph restating the offer of screening in simple language. We undertook a cluster-randomised trial of all 168 480 individuals who were due to receive a reminder over 20 days in 2013. Randomisation was based on the day of invitation. Blinding of individuals was not possible, but the possibility of bias was minimal owing to the lack of direct contact with participants. The enhanced reminder was sent to 78 067 individuals and 90 413 received the usual reminder. The primary outcome was the proportion of people adequately screened and its variation by quintile of Index of Multiple Deprivation. Data were analysed by logistic regression with conservative variance estimates to take account of cluster randomisation. Results: There was a small but statistically significant ( P ¼ 0.001) increase in participation with the enhanced reminder (25.8% vs 25.1%). There was significant ( P ¼ 0.005) heterogeneity of the effect by socioeconomic status with an 11% increase in the odds of participation in the most deprived quintile (from 13.3 to 14.1%) and no increase in the least deprived. We estimated that implementing the enhanced reminder nationally could result in up to 80 more people with high or intermediate risk colorectal adenomas and up to 30 more cancers detected each year if it were implemented nationally. The intervention incurred a small one- off cost of d 78 000 to modify the reminder letter. Conclusions: The enhanced reminder increases overall uptake and reduces the socioeconomic gradient in bowel cancer screening participation at little additional cost.

Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake.Participants. 150,417 adults (59–74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013.Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES).Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81–1.06;p=0.27). There was no interaction between group and SES quintile (p=0.44).Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour.

Summary Background Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening. Methods All people eligible for screening (men and women aged 60–74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing people's stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July–August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020. Findings As all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0·5%). Trials 1 (n=163 525) and 2 (n=150 417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio [OR] 1·07, 95% CI 1·04–1·10, p

Background: There is a socioeconomic gradient in the uptake of screening in the English NHS Bowel Cancer Screening Programme (BCSP), potentially leading to inequalities in outcomes. We tested whether endorsement of bowel cancer screening by an individual's general practice (GP endorsement; GPE) reduced this gradient. Methods: A cluster-randomised controlled trial. Over 20 days, individuals eligible for screening in England from 6480 participating general practices were randomly allocated to receive a GP-endorsed or the standard invitation letter. The primary outcome was the proportion of people adequately screened and its variation by quintile of Index of Multiple Deprivation. Results: We enrolled 265 434 individuals. Uptake was 58.2% in the intervention arm and 57.5% in the control arm. After adjusting for age, sex, hub and screening episode, GPE increased the overall odds of uptake (OR=1.07, 95% CI 1.04–1.10), but did not affect its socioeconomic gradient. We estimated that implementing GPE could result in up to 165 more people with high or intermediate risk colorectal adenomas and 61 cancers detected, and a small one-off cost to modify the standard invitation (£78 000). Conclusions: Although GPE did not improve its socioeconomic gradient, it offers a low-cost approach to enhancing overall screening uptake within the NHS BCSP.

Introduction With increasing demand for colonoscopy in the NHS Bowel Cancer Screening Programme (BCSP) in England, there is a need for effective non-colonoscopic approaches to surveillance. We have undertaken a study to compare the sensitivity and specificity of a faecal immunochemical test for haemoglobin (FIT) annually for three years with colonoscopy surveillance, in patients diagnosed with intermediate-risk adenomas following a positive faecal occult blood test in the BCSP. Methods Participants are invited to complete a FIT (OC-SENSOR, Eiken Chemical Co. Ltd.) annually while awaiting their first surveillance colonoscopy. Those testing positive (>40 µg Hb/g faeces) are invited to have their three-year colonoscopy brought forward, while those testing negative are sent another FIT a year later until they have completed three rounds of testing. We aim to determine the sensitivity of FIT in detecting colorectal cancer or advanced adenomas (≥10 mm, or with tubulovillous or villous histology, or with high-grade dysplasia), using colonoscopy as the reference standard. Results We invited 8009 people to participate in the study, of whom 5840 (72.9%) consented. The positivity rate in Round 1 was 5.8% (336/5840). To date, 265/303 (87.5%) have had an early colonoscopy: 62/265 (23.4%) had advanced adenomas and five (1.9%) had cancer. 33/336 (9.8%) declined an early colonoscopy. To date, in Round 2 we have invited 2800 patients who tested FIT negative in Round 1: 2560 (91.4%) completed a second FIT and 115/2560 (4.5%) tested positive. 85/106 (80.2%) have received an early colonoscopy: 13/85 (15.3%) had advanced adenomas and two (2.4%) had cancer. 9/115 (7.8%) declined an early colonoscopy. A total of 2445 participants had negative FIT tests in Rounds 1 and 2 and will be invited to complete a final FIT, prior to their surveillance colonoscopy. Satisfaction with the study was high among those who completed a questionnaire, with 95.4% (4177/4378) of FIT-negative and 91% (203/223) of FIT-positive participants in Round 1 stating that they would complete another kit in future. Conclusion Compliance with the study was high, and the majority of participants reported that they would use FIT again. Almost a quarter (23.4%) of patients in Round 1 who had an early colonoscopy had advanced adenomas, falling to 15.3% in Round 2. Round 2 is ongoing, with Round 3 starting in January 2014. Disclosure of Interest None Declared.