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Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients. We aimed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk. We did a randomised, double-blind, placebo-controlled trial to compare aspirin (75 mg/day) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day. Duration of treatment and follow-up was 18 months. The primary endpoint was a composite of ischaemic stroke, myocardial infarction, vascular death, or rehospitalisation for acute ischaemia (including rehospitalisation for transient ischaemic attack, angina pectoris, or worsening of peripheral arterial disease). Analysis was by intention to treat, using logrank test and a Cox's proportional-hazards model. 596 (15.7%) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 (16·7%) in the clopidogrel alone group (relative risk reduction 6.4%, [95% CI −4·6 to 16·3]; absolute risk reduction 1% [−0·6 to 2·7]). Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone (96 [2·6%] vs 49 [1·3%]; absolute risk increase 1·3% [95% CI 0·6 to 1·9]). Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality. Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events. However, the risk of life-threatening or major bleeding is increased by the addition of aspirin.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity likely related to altered processing of sensory stimuli along the brain-gut axis. Previous neuroimaging studies demonstrated structural and functional alteration of several brain areas involved in bodily representation, e.g. the insula, in patients with IBS. By means of resting-state functional magnetic resonance imaging (rs-fMRI) we searched for alteration of functional connectivity within the network involved in self-bodily consciousness. We found significant inverse correlation between hypochondriasis assessed through a clinical questionnaire and connectivity between posterior cingulate cortex and left supramarginal gyrus, extending into the adjacent superior temporal gyrus. Moreover, we observed a significant and positive correlation between a clinical questionnaire assessing interoception and connectivity between left anterior ventral insula and two clusters located in supramarginal gyrus bilaterally. Our findings highlight an “abnormal network synchrony” reflecting functional alteration, in the absence of structural and micro-structural changes, which might represent a possible therapeutic target for Irritable Bowel Syndrome.

BackgroundRheumatoid arthritis (RA) associates with higher mortality rates than general population, mostly due to cardiovascular (CV) disease [1]. Guidelines recommend CV risk assessment in all RA patients. The European League against Rheumatism (EULAR) has proposed a modified version of SCORE risk estimation system (mSCORE) [2]. Few studies assessed the impact of an increased carotid intima media thickness (cIMT), carotid plaques, and ankle-brachial index (ABI) on the CV risk assessment in patients with RA.ObjectivesTo assess whether the value of carotid ultrasonography and ABI in the stratification of CV risk in RA.MethodsAll RA patients who consecutively attended the outpatient rheumatology clinic of our hospital were enrolled. Exclusion criteria: diabetes mellitus, history of cardio and cerebrovascular events and age>75 years old.ResultsThe study population was represented by 78 patients, 61 women (78.2%), median age 60 years old and disease duration 6.0 years. The SCORE (median) and EULAR mSCORE were 1.25 and 1.5.Table 1.ABI and carotid ultrasound findings according to CV risk stratificationSCORE CV risk (n)mSCOREAbnormal ABIcIMT >0.90 mmCarotid plaquescIMT >0.90 mm and/or carotid plaquesLow (23)232/23 (17.4)0/23 (0.0%)0/23 (0.0%)0/23 (0.0%)Moderate (48472/47 (4.3%)3/47 (6.4%)15/47 (31.9%)15/47 (31.9%)High (7)80/8 (0.0%)1/8 (12.5%)4/8 (50.0%)4/8 (50.0%)Total (78)784/78 (5.1%)4/78 (5.1%)19/78 (24.4%)19/78 (24.4%)All patients with an abnormal ABI had a normal cIMT. 27/78 (34.6%) patients had High CV risk defined as a)mSCORE ≥5% or b)mSCORE<5% plus cIMT>0.90 mm and/or plaques or an abnormal ABI. A SCORE>5% had a Sensitivity of 29.6% (8/27), an Abnormal ABI 14.8% (4/27), a cIMT>0.90mm plus carotid plaques 70.4% (19/27), a mSCORE<5% plus Abnormal ABI 14.8% (4/27), a mSCORE<5% plus cIMT>0.90mm and/or carotid plaques 55.6% (15/27) and an Abnormal ABI plus cIMT>0.90mm and/or carotid plaques 85.2% (23/27).ConclusionsSCORE showed a low sensitivity to identify high risk RA patients, and mSCORE did not improve it. Carotid ultrasonography assessment showed a higher sensitivity than mSCORE and ABI to detect high CV risk. Despite its low sensitivity, an abnormal ABI identify high risk patients not discriminated by using mSCORE nor cIMT. Carotid ultrasound seems to be more sensitive than ABI, SCORE and mSCORE to identify high CV risk in patients with RA.ReferencesGibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care 2012; 18: S295-S302.Peters MJ, Symmons DP, McCarey D, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010;69:325e31.Disclosure of InterestNone declared

Background: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are restricted to KRAS wild-type (WT) metastatic colorectal cancers (mCRCs), usually identified by direct sequencing, that may yield false negative results because of genetic heterogeneity within the tumour. We evaluated the efficiency of high-resolution melting analysis (HRMA) in identifying KRAS- mutant (MUT) tumours. Methods: We considered 50 mCRC patients scored as KRAS- WT by direct sequencing and treated with cetuximab-containing chemotherapy, and tested the correlations between HRMA findings and response rate (RR), progression-free (PFS) and overall survival (OS). Results: Aberrant melting curves were detected in four (8%) cases; gene cloning confirmed these mutations. Response rate (RR) of HRMA KRAS -WT patients was 28.3%. There was no response in HRMA KRAS- MUT patients. Disease control rate (responsive plus stable disease) was 58.7% in HRMA KRAS- WT patients and 25% in HRMA KRAS- MUT patients. There was no correlation between HRMA KRAS status and RR ( P =0.287) or disease control ( P =0.219). Median PFS (4.8 vs 2.3 months; hazard ratio (HR)=0.29, P =0.02) and OS (11.0 vs 2.7 months; HR=0.11, P =0.03) were significantly longer for the HRMA KRAS- WT than for HRMA KRAS- MUT patients. Conclusions: High-resolution melting analysis identified 8% more KRAS -MUT patients not responding to cetuximab-containing regimens, suggesting that HRMA may be more effective than direct sequencing in selecting patients for anti-EGFR antibodies.

Thromboprophylaxis with low-molecular-weight heparin is known to prevent deep-vein thrombosis in acutely ill medical patients. This large trial showed no effect of enoxaparin on 30-day mortality, which was virtually identical in the active-treatment and placebo groups. Venous thromboembolism is an important complication in hospitalized patients. 1 – 4 It is estimated that if thromboprophylaxis is not administered, objectively diagnosed deep-vein thrombosis — with the potential for fatal pulmonary embolism — will develop in 10 to 20% of medical patients and in 40 to 60% of patients undergoing major orthopedic surgery. 5 A retrospective review of 6833 autopsies showed that 81% of fatal cases of pulmonary embolism occurred in nonsurgical patients. 6 Pharmacologic thromboprophylaxis has been proved to reduce the incidence of venous thromboembolism in both surgical patients and acutely ill medical patients. 5 , 7 – 9 In surgical patients, thromboprophylaxis has been . . .

Background: The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial. Methods: MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient. Results: Enrolment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence. Conclusion: MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.

Sophisticated evidence-based information resources can filter medical evidence from the literature, integrate it into electronic health records, and generate recommendations tailored to individual patients. To assess the effectiveness of a computerized clinical decision support system (CDSS) that preappraises evidence and provides health professionals with actionable, patient-specific recommendations at the point of care. Open-label, parallel-group, randomized clinical trial among internal medicine wards of a large Italian general hospital. All analyses in this randomized clinical trial followed the intent-to-treat principle. Between November 1, 2015, and December 31, 2016, patients were randomly assigned to the intervention group, in which CDSS-generated reminders were displayed to physicians, or to the control group, in which reminders were generated but not shown. Data were analyzed between February 1 and July 31, 2018. Evidence-Based Medicine Electronic Decision Support (EBMEDS), a commercial CDSS covering a wide array of health conditions across specialties, was integrated into the hospital electronic health records to generate patient-specific recommendations. The primary outcome was the resolution rate, the rate at which medical problems identified and alerted by the CDSS were addressed by a change in practice. Secondary outcomes included the length of hospital stay and in-hospital all-cause mortality. In this randomized clinical trial, 20 563 patients were admitted to the hospital. Of these, 6480 (31.5%) were admitted to the internal medicine wards (study population) and randomized (3242 to CDSS and 3238 to control). The mean (SD) age of patients was 70.5 (17.3) years, and 54.5% were men. In total, 28 394 reminders were generated throughout the course of the trial (median, 3 reminders per patient per hospital stay; interquartile range [IQR], 1-6). These messages led to a change in practice in approximately 4 of 100 patients. The resolution rate was 38.0% (95% CI, 37.2%-38.8%) in the intervention group and 33.7% (95% CI, 32.9%-34.4%) in the control group, corresponding to an odds ratio of 1.21 (95% CI, 1.11-1.32; P < .001). The length of hospital stay did not differ between the groups, with a median time of 8 days (IQR, 5-13 days) for the intervention group and a median time of 8 days (IQR, 5-14 days) for the control group (P = .36). In-hospital all-cause mortality also did not differ between groups (odds ratio, 0.95; 95% CI, 0.77-1.17; P = .59). Alert fatigue did not differ between early and late study periods. An international commercial CDSS intervention marginally influenced routine practice in a general hospital, although the change did not statistically significantly affect patient outcomes. ClinicalTrials.gov identifier: NCT02577198.

The SIRIO study collected detailed information on the stroke care of patients treated in neurological departments in Italy. This report refers to the baseline profile of patients. Each centre recorded the incident cases of ischaemic and haemorrhagic stroke, excluding SAH, for 1-4 months. Baseline data include demographics, risk factors, comorbidities, pre-event medications, social conditions, NIHSS and Rankin scale on entry, Barthel Index pre-event, diagnostic tests and treatments applied on entry. Overall, 3018 patients (56.7% men; mean age 72.1+/-12.2 years) with ischaemic (85.3%) or haemorrhagic stroke were hospitalised in 103 centres; 51% arrived by ambulance. Median time to hospital was 140 min (RIQ: 60-615). TOAST classification of the 2573 ischaemic strokes was: 29.4% large-artery atherosclerosis, 24.6% cardioembolic, 26.2% small vessels occlusion, 6.5% other determined causes and 13.3% undetermined. CT and/or MR were performed in all patients. Total Greenfield's comorbidity score was 5.4+/-3.5. Mean Barthel Index pre-event was 93+/-17; Rankin score on entry was 4-5 in 48% of the patients and 0-1 in 25%. Mean NIHSS on entry was 7.1+/-5.4; 52% of the patients had a NHISS <6 and 1% >22. SIRIO began giving the expected insights on the in-hospital management of stroke in Italy. Further information will be provided by the longitudinal phase of the study, which is in progress. Pre-event patient management and mode of reporting call for additional educational actions.