Explore the vast range of titles available.

Everolimus-eluting stent (EES) reduces the risk of restenosis in elective percutaneous coronary intervention. However, the use of drug-eluting stent in patients with ST-segment elevation myocardial infarction (STEMI) is still controversial. Data regarding the performance of second-generation EES in this setting are scarce. We report the 1-year result of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) trial, comparing EES with bare-metal stents (BMS) in patients with STEMI. This multicentre, prospective, randomised, all-comer controlled trial was done in 12 medical centres in three countries. Between Dec 31, 2008, and May 15, 2010, we recruited patients with STEMI up to 48 h after the onset of symptoms requiring emergent percutaneous coronary intervention. Patients were randomly assigned (ratio 1:1) to receive EES or BMS. Randomisation was in blocks of four or six patients, stratified by centre and centralised by telephone. Patients were masked to treatment. The primary endpoint was the patient-oriented combined endpoint of all-cause death, any recurrent myocardial infarction, and any revascularisation at 1 year and was analysed by intention to treat. The secondary endpoints of the study included the device-oriented combined endpoint of cardiac death, target vessel myocardial infarction or target lesion revascularisation, and rates of all cause or cardiac death, recurrent myocardial infarction, target lesion or target vessel revascularisation, stent thrombosis, device and procedure success, and major and minor bleeding. This trial is registered with ClinicalTrials.gov, number NCT00828087. Of the 1504 patients randomised, 1498 patients were randomly assigned to receive EES (n=751) or BMS (n=747). The primary endpoint was similar in both groups (89 [11·9%] of 751 patients in the EES group vs 106 [14·2%] of 747 patients in the BMS group; difference −2·34 [95% CI −5·75 to 1·07]; p=0·19). Device-oriented endpoint (44 [5·9%] in the EES group vs 63 [8·4%] in the BMS group; difference −2·57 [95% CI −5·18 to 0·03]; p=0·05) did not differ between groups, although rates of target lesion and vessel revascularisation were significantly lower in the EES group (16 [2·1%] vs 37 [5·0%], p=0·003, and 28 [3·7%] vs 51 [6·8%], p=0·0077, respectively). Rates of all cause (26 [3·5%] for EES vs 26 [3·5%] for BMS, p=1·00) or cardiac death (24 [3·2%] for EES vs 21 [2·8%] for BMS, p=0·76) or myocardial infarction (10 [1·3%] vs 15 [2·0%], p=0·32) did not differ between groups. Stent thrombosis rates were significantly lower in the EES group (4 [0·5%] patients with definite stent thrombosis in the EES group vs 14 [1·9%] in the BMS group and seven [0·9%] patients with definite or probable stent thrombosis in the EES group vs 19 [2·5%] in the BMS group, both p=0·019). Although device success rate was similar between groups, procedure success rate was significantly higher in the EES group (731 [97·5%] vs 705 [94·6%]; p=0·0050). Finally, Bleeding rates at 1 year were comparable between groups (29 [3·9%] patients in the EES group vs 39 [5·2%] in the BMS group; p=0·19). The use of EES compared with BMS in the setting of STEMI did not lower the patient-oriented endpoint. However, at the stent level both rates of target lesion revascularisation and stent thrombosis were reduced in recipients of EES. Spanish Heart Foundation.

The aim of this study was to validate a molecular classification of colorectal cancer (CRC) based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP) status, BRAF, and KRAS and investigate each subtype's response to chemotherapy. This retrospective observational study included a population-based cohort of 878 CRC patients. We classified tumours into five different subtypes based on BRAF and KRAS mutation, CIMP status, and MSI. Patients with advanced stage II (T4N0M0) and stage III tumours received 5-fluoruracil (5-FU)-based chemotherapy or no adjuvant treatment based on clinical criteria. The main outcome was disease-free survival (DFS). Patients with the combination of microsatellite stable (MSS) tumours, BRAF mutation and CIMP positive exhibited the worst prognosis in univariate (log rank P<0.0001) and multivariate analyses (hazard ratio 1.75, 95% CI 1.05-2.93, P = 0.03) after adjusting for age, sex, chemotherapy, and TNM stage. Treatment with 5-FU-based regimens improved prognosis in patients with the combination of MSS tumours, KRAS mutation and CIMP negative (log rank P = 0.003) as well as in patients with MSS tumours plus BRAF and KRAS wild-type and CIMP negative (log-rank P<0.001). After adjusting for age, sex, and TNM stage in the multivariate analysis, only patients with the latter molecular combination had independently improved prognosis after adjuvant chemotherapy (hazard ratio 2.06, 95% CI 1.24-3.44, P = 0.005). We confirmed the prognostic value of stratifying CRC according to molecular subtypes using MSI, CIMP status, and somatic KRAS and BRAF mutation. Patients with traditional chromosomally unstable tumours obtained the best benefit from adjuvant 5-FU-based chemotherapy.

ObjectivesTo evaluate the cost-effectiveness of the ST-segment elevation myocardial infarction (STEMI) network of Catalonia (Codi Infart).DesignCost-utility analysis.SettingThe analysis was from the Catalonian Autonomous Community in Spain, with a population of about 7.5 million people.ParticipantsPatients with STEMI treated within the autonomous community of Catalonia (Spain) included in the IAM CAT II-IV and Codi Infart registries.Outcome measuresCosts included hospitalisation, procedures and additional personnel and were obtained according to the reperfusion strategy. Clinical outcomes were defined as 30-day avoided mortality and quality-adjusted life-years (QALYs), before (N=356) and after network implementation (N=2140).ResultsA substitution effect and a technology effect were observed; aggregate costs increased by 2.6%. The substitution effect resulted from increased use of primary coronary angioplasty, a relatively expensive procedure and a decrease in fibrinolysis. Primary coronary angioplasty increased from 31% to 89% with the network, and fibrinolysis decreased from 37% to 3%. Rescue coronary angioplasty declined from 11% to 4%, and no reperfusion from 21% to 4%. The technological effect was related to improvements in the percutaneous coronary intervention procedure that increased efficiency, reducing the average length of the hospital stay. Mean costs per patient decreased from €8306 to €7874 for patients with primary coronary angioplasty. Clinical outcomes in patients treated with primary coronary angioplasty did not change significantly, although 30-day mortality decreased from 7.5% to 5.6%. The incremental cost-effectiveness ratio resulted in an extra cost of €4355 per life saved (30-day mortality) and €495 per QALY. Below a cost threshold of €30 000, results were sensitive to variations in costs and outcomes.ConclusionsThe Catalan STEMI network (Codi Infart) is cost-efficient. Further studies are needed in geopolitical different scenarios.

ST-elevation myocardial infarctions (STEMI) caused by proximal left-anterior descending (LAD) lesions have more myocardium at risk and worse outcomes than those located in other segments. The aim is to compare outcomes of patients with STEMI and proximal-LAD lesions treated with bare-metal stents (BMS) versus everolimus-eluting stents (EES). The EXAMINATION trial randomized 1498 STEMI patients to BMS versus EES. The primary end point was the patient-oriented combined of all-cause death, any-recurrent myocardial infarction (MI) and any-revascularization. The secondary end point included the device-oriented combined of cardiac death, target-vessel MI and target-lesion revascularization (TLR). STEMI with a proximal-LAD occlusion was observed in 290 patients (BMS = 132 and EES = 158). Both groups were similar except for diabetes (12.9% vs 24.1%; P = .016). At 1 year, the primary end point was observed in 18.9% and 9.5% of patients treated with BMS and EES, respectively (P = .023). The secondary end point was observed in 11.4% and 5.1%, respectively (P = .053). There were no differences in cardiac death (4.5% vs 3.8%; P = .750) and MI (1.5% vs 0%; P = .121). BMS had higher rate of TLR compared to EES (6.8% vs 1.3%; P = .014). Patients with proximal-LAD STEMI had higher mortality than patients with non proximal-LAD STEMI (5.5% vs 2.9%; P = .027). Proximal-LAD lesions treated with BMS tended to increase the risk of the primary end point compared with other segments (18.9% vs 13.0%; P = .079). However, EES implanted in proximal-LAD had similar outcomes compared with other locations (9.5% vs 12.0%; P = .430). Adjusting for confounders, the interaction between BMS and proximal-LAD location was associated with the primary end point. Patients with STEMI and proximal-LAD lesions treated with EES have better outcomes compared with BMS at 1 year. Although further investigations are required, it seems reasonable to consider EES for proximal-LAD STEMI-lesions.

ST-elevation myocardial infarctions (STEMI) caused by proximal left-anterior descending (LAD) lesions have more myocardium at risk and worse outcomes than those located in other segments. The aim is to compare outcomes of patients with STEMI and proximal-LAD lesions treated with bare-metal stents (BMS) versus everolimus-eluting stents (EES). The EXAMINATION trial randomized 1498 STEMI patients to BMS versus EES. The primary end point was the patient-oriented combined of all-cause death, any-recurrent myocardial infarction (MI) and any-revascularization. The secondary end point included the device-oriented combined of cardiac death, target-vessel MI and target-lesion revascularization (TLR). STEMI with a proximal-LAD occlusion was observed in 290 patients (BMS = 132 and EES = 158). Both groups were similar except for diabetes (12.9% vs 24.1%; P = .016). At 1 year, the primary end point was observed in 18.9% and 9.5% of patients treated with BMS and EES, respectively (P = .023). The secondary end point was observed in 11.4% and 5.1%, respectively (P = .053). There were no differences in cardiac death (4.5% vs 3.8%; P = .750) and MI (1.5% vs 0%; P = .121). BMS had higher rate of TLR compared to EES (6.8% vs 1.3%; P = .014). Patients with proximal-LAD STEMI had higher mortality than patients with non proximal-LAD STEMI (5.5% vs 2.9%; P = .027). Proximal-LAD lesions treated with BMS tended to increase the risk of the primary end point compared with other segments (18.9% vs 13.0%; P = .079). However, EES implanted in proximal-LAD had similar outcomes compared with other locations (9.5% vs 12.0%; P = .430). Adjusting for confounders, the interaction between BMS and proximal-LAD location was associated with the primary end point. Patients with STEMI and proximal-LAD lesions treated with EES have better outcomes compared with BMS at 1 year. Although further investigations are required, it seems reasonable to consider EES for proximal-LAD STEMI-lesions.

Background Paracetamol’s solubility is achieved by adding to the excipient sodium salts, either as bicarbonate, carbonate or citrate. As the relationship between salt and hypertension is well known, due to the sodium content it has raised a hypothesis that may interfere with the control of that risk factor. Therefore, the objective of this study is to evaluate the effect on blood pressure of effervescent paracetamol compared to non-effervescent, in hypertensive patients. Methods/Design This is the protocol of a phase IV multicenter clinical trial, randomized, controlled, crossover, open, which will compare the effect of two different formulations of paracetamol (effervescent or non-effervescent) in the blood pressure of hypertensive patients, with a seven weeks follow up. 49 controlled hypertensive patients will be included (clinical BP lower than 150 and 95 mmHg, and lower than 135 mmHg and 85 mmHg in patients with diabetes or a history of cardiovascular event, and daytime ambulatory measurements lower than 140 and 90 mmHg) and mild to moderate pain (Visual Analog Scale between 1 and 4). The study was approved by the ethics committee of the Fundació Jordi Gol i Gurina and following standards of good clinical practice. The primary endpoint will be the variations in systolic BP in 24 h Ambulatory Blood Pressure Monitoring, considering significant differences 2 or more mmHg among those treated with non-effervescent and effervescent formulations. Intention-to-treat and per-protocol analysis will be held. Discussion Despite the broad recommendation not to use effervescent drugs in patients with hypertension, there are relatively little studies that show exactly this pressor effect due to sodium in salt that gives the effervescence of the product. This is the first clinical trial designed to study the effect of effervescence compared to the non-effervescent, in well-controlled hypertensive patients with mild to moderate pain, performed in routine clinical practice Trial registration NCT 02514538