The CEA Second-Look Trial: a randomised controlled trial of carcinoembryonic antigen prompted reoperation for recurrent colorectal cancer

Objective In patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit?Design A randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative.Setting 58 hospitals in the UK.Participants From 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms.Interventions ‘Second-look’ surgery with intention to remove any recurrence discovered.Primary outcome measure Survival.Results By February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival.Conclusions The trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years.Trial registration number ISRCTN76694943

Current misconception 3: that subgroup-specific trial mortality results often provide a good basis for individualising patient care

Misconceptions and ill-founded theories can arise in all areas of science. However, the apparent accessibility of many epidemiology findings and popular interest in the subject can lead to additional misunderstandings. The article below is the third in an occasional series of short editorials highlighting some current misinterpretations of epidemiological findings. Invited authors will be given wide scope in judging the prevalence of the misconception under discussion. We hope that this series will prove instructive to cancer researchers in other disciplines as well as to students of epidemiology. Adrian L Harris and Leo Kinle

A cluster randomised trial to assess the impact of clinical pathways on AMI management in rural Australian emergency departments

Background. People living in rural Australia are more likely to die in hospital following an acute myocardial infarction than those living in major cities. While several factors, including time taken to access hospital care, contribute to this risk, it is also partially attributable to the lower uptake of evidence-based guidelines for the administration of thrombolytic drugs in rural emergency departments where up to one-third of eligible patients do not receive this life-saving intervention. Clinical pathways have the potential to link evidence to practice by integrating guidelines into local systems, but their impact has been hampered by variable implementation strategies and sub-optimal research designs. The purpose of this study is to determine the impact of a five-step clinical pathways implementation process on the timely and efficient administration of thrombolytic drugs for acute myocardial infarctions managed in rural Australian emergency departments. Methods/Design. The design is a two-arm, cluster-randomised trial with rural hospital emergency departments that treat and do not routinely transfer acute myocardial infarction patients. Six rural hospitals in the state of Victoria will participate, with three in the intervention group and three in the control group. Intervention hospitals will participate in a five-step clinical pathway implementation process: engagement of clinicians, pathway development according to local resources and systems, reminders, education, and audit and feedback. Hospitals in the control group will each receive a hard copy of Australian national guidelines for chest pain and acute myocardial infarction management. Each group will include 90 cases to give a power of 80% at 5% significance level for the two primary outcome measures: proportion of those eligible for thrombolysis receiving the drug and time to delivery of thrombolytic drug. Discussion. Improved compliance with thrombolytic guidelines via clinical pathways will increase acute myocardial infarction survival rates in rural hospitals and thereby help to reduce rural-urban mortality inequalities. Such knowledge translation has the potential to be adapted for a range of clinical problems in a wide array of settings. Trial registration. Australia New Zealand Clinical Trials Registry code ACTRN12608000209392

Spontaneous recanalization of a completely occluded saphenous vein graft two months following acute myocardial infarction with persistent one year patency

Acute myocardial infarction resulting from saphenous vein graft occlusion occurs not infrequently in patients who have undergone coronary artery bypass graft surgery. In this case report, we present a novel case of spontaneous recanalization of a thrombotic graft occlusion in a patient who presented with a subacute myocardial infarction. The patient was treated medically with aspirin as the only anti-platelet agent. Interestingly, he presented 2 months later with new onset angina. Coronary angiography demonstrated complete resolution of thrombus but a severe focal stenosis in the distal anastomoses. Following drug eluting stent placement, a favorable clinical course has ensued and patency confirmed on follow up angiography at 1 year

A randomised controlled trial to evaluate and optimize the use of antiplatelet agents in the perioperative management in patients undergoing general and abdominal surgery- the APAP trial (ISRCTN45810007)

<p>Abstract</p> <p>Background</p> <p>Due to the increase of cardiovascular diseases acetylsalicylic acid (ASA) has become one of the most frequently prescribed drugs these days. Despite the rising number of patients with ASA medication presenting for elective general and abdominal surgery and the potentially increased risk of hemorrhage in these patients, there are no clear, evidence-based guidelines for the perioperative use of antiplatelet agents. The present randomised controlled trial was designed to evaluate the safety and optimize the use of ASA in the perioperative management of patients undergoing general and abdominal surgery.</p> <p>Methods/Design</p> <p>This is a two-arm, monocenter randomised controlled trial. Patients scheduled for elective surgical treatment (i.e. inguinal hernia repair, cholecystectomy and colorectal resections) with ASA as a permanent medication are randomised equally to perioperative continuation or discontinuation of ASA. Patients who are randomised in the discontinuation group stop the administration of ASA five days prior to surgical treatment and start intake of ASA on postoperative day 5. Fifty-two patients will be enrolled in this trial. The primary outcome is the incidence of postoperative bleeding and cardiovascular events at 30 days after surgery. In addition a set of general as well as surgical variables are analysed.</p> <p>Discussion</p> <p>This is a randomised controlled two-group parallel trial designed to assess the safety and optimize the use of ASA in the perioperative management of patients undergoing general and abdominal surgery. The results of this pilot study build the basis for a confirmative randomised controlled trial that may help to clarify the use and potential risk/benefits of perioperative ASA medication in patients undergoing elective surgery.</p> <p>Trial registration</p> <p>The trial is registered with Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN45810007">ISRCTN45810007</a>.</p

Differences in access to coronary care unit among patients with acute myocardial infarction in Rome: old, ill, and poor people hold the burden of inefficiency

BACKGROUND: Direct admission to Coronary Care Unit (CCU) on hospital arrival can be considered as a good proxy for adequate management in patients with acute myocardial infarction (AMI), as it has been associated with better prognosis. We analyzed a cohort of patients with AMI hospitalized in Rome (Italy) in 1997–2000 to assess the proportion directly admitted to CCU and to investigate the effect of patient characteristics such as gender, age, illness severity on admission, and socio-economic status (SES) on CCU admission practices. METHODS: Using discharge data, we analyzed a cohort of 9127 AMI patients. Illness severity on admission was determined using the Deyo's adaptation of the Charlson's comorbidity index, and each patient was assigned to one to four SES groups (level I referring to the highest SES) defined by a socioeconomic index, derived by the characteristics of the census tract of residence. The effect of gender, age, illness severity and SES, on risk of non-admission to CCU was investigated using a logistic regression model (OR, CI 95%). RESULTS: Only 53.9% of patients were directly admitted to CCU, and access to optimal care was more frequently offered to younger patients (OR = 0.35; 95%CI = 0.25–0.48 when comparing 85+ to >=50 years), those with less severe illness (OR = 0.48; 95%CI = 0.37–0.61 when comparing Charlson index 3+ to 0) and the socially advantaged (OR = 0.81; 95%CI = 0.66–0.99 when comparing low to high SES). CONCLUSION: In Rome, Italy, standard optimal coronary care is underprovided. It seems to be granted preferentially to the better off, even after controversial clinical criteria, such as age and severity of illness, are taken into account

Pre-hospital ECG for acute coronary syndrome in urban India: A cost-effectiveness analysis

<p>Abstract</p> <p>Background</p> <p>Patients with acute coronary syndrome (ACS) in India have increased pre-hospital delay and low rates of thrombolytic reperfusion. Use of ECG could reduce pre-hospital delay among patients who first present to a general practitioner (GP). We assessed whether performing ECG on patients with acute chest pain would improve long-term outcomes and be cost-effective.</p> <p>Methods</p> <p>We created a Markov model of urban Indian patients presenting to a GP with acute chest pain to compare a GP's performing an ECG versus not performing one. Variables describing the accuracy of a GP's referral decision in chest pain and ACS, ACS treatment patterns, the effectiveness of thrombolytic reperfusion, and costs were derived from Indian data where available and other developed world studies. The model was used to estimate the incremental cost-effectiveness ratio (ICER) of the intervention in 2007 US dollars per quality adjusted life years (QALY) gained.</p> <p>Results</p> <p>Under baseline assumptions, the ECG strategy cost an additional $12.65 per QALY gained compared to no ECG. Sensitivity analyses around the cost of the ECG, cost of thrombolytic, and referral accuracy of the GP yielded ICERs for the ECG strategy ranging between cost-saving and$1124/QALY. All results indicated the intervention is cost-effective under current World Health Organization recommendations.</p> <p>Conclusions</p> <p>While direct presentation to the hospital with acute chest pain is preferable, in urban Indian patients presenting first to a GP, an ECG performed by the GP is a cost-effective strategy to reduce disability and mortality. This strategy should be clinically studied and considered until improved emergency transport services are available.</p

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

Performance of missing transverse momentum reconstruction in proton-proton collisions at root s=13 TeV using the CMS detector

The performance of missing transverse momentum ((p) over right arrow (miss)(T)) reconstruction algorithms for the CMS experiment is presented, using proton-proton collisions at a center-of-mass energy of 13 TeV, collected at the CERN LHC in 2016. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The results include measurements of the scale and resolution of (p) over right arrow (miss)(T), and detailed studies of events identified with anomalous (p) over right arrow (miss)(T). The performance is presented of a (p) over right arrow (miss)(T) reconstruction algorithm that mitigates the effects of multiple proton-proton interactions, using the "pileup per particle identification" method. The performance is shown of an algorithm used to estimate the compatibility of the reconstructed (p) over right arrow (miss)(T) with the hypothesis that it originates from resolution effects.Peer reviewe