Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

The tuning fork test—a useful tool for improving specificity in “Ottawa positive” patients after ankle inversion injury

The Ottawa ankle rules are a clinical instrument calibrated towards a high sensitivity in order not to miss any fractures of the ankle or mid‐foot. This is at the cost of a mean specificity of around only 32%. The aim of this study was to determine the suitability of tuning fork testing in combination with existing Ottawa guidance for increasing the specificity in detecting fractures of the lateral malleolus. A prospective pilot study was carried out, in which a single trained investigator examined all patients with already “Ottawa positive” findings for possible lateral malleolus injury by applying a tuning fork (C° 128 Hz). The tuning fork test findings were compared with formal reports of plain ankle radiographs using simple cross‐table analysis. The observed prevalence of ankle fractures was 5 of 49 (10%). Sensitivity and specificity were calculated as 100% and 61%, respectively, for tuning fork testing on the tip of the lateral malleolus (TLM), and as 100% and 95%, respectively, for testing on the distal fibula shaft (DFS). The associated positive and negative likelihood ratios were 2.59 and 0 (TLM), and 22 and 0 (DFS), respectively. The data were significant, with p = 0.014 (TLM) and p<0.001 (DFS). This study suggests that additional tuning fork testing of “Ottawa positive” patients may lead to a marked reduction in ankle radiographs, with consequently reduced radiation exposure and journey time. This may be particularly relevant in situations where radiological facilities are not readily available (expedition medicine) or where access to these has to be prioritised (major incidents, natural catastrophes)

Low-dose methoxyflurane analgesia in adolescent patients with moderate-to-severe trauma pain: a subgroup analysis of the STOP! study

Stuart Hartshorn,1 Patrick Dissmann,2 Frank Coffey,3 Mark Lomax4 1Emergency Department, Birmingham Children&rsquo;s Hospital, Birmingham, UK; 2Academic Department of Emergency Medicine, James Cook University Hospital, Middlesbrough, UK; 3DREEAM: Department of Research and Education in Emergency Medicine, Acute Medicine and Major Trauma, Nottingham University Hospitals NHS Trust, Nottingham, UK; 4Data Management &amp; Statistics, Mundipharma Research Limited, Cambridge, UK Introduction: The undertreatment of acute pain presents a significant challenge in the Emergency Department. This post hoc subgroup analysis of a previously reported randomized controlled UK study reports the efficacy and safety of low-dose methoxyflurane analgesia in treating adolescent patients with moderate-to-severe trauma pain. Patients and methods: Three hundred patients (96 in the adolescent subgroup) aged &ge;12 years requiring analgesia for acute trauma pain (pain score of 4&ndash;7 on the Numerical Rating Scale) at triage were randomized 1:1 to methoxyflurane (up to 6 mL) or placebo (normal saline), both administered using a Penthrox&reg; inhaler. The patient could request rescue medication (paracetamol/opioids) at any time. The primary endpoint was the change from baseline in visual analog scale (VAS) pain intensity. Results: Mean VAS pain score for the adolescent subgroup at baseline was ~61 mm. Adjusted mean change in VAS pain intensity from baseline to 5, 10, 15, and 20 minutes was &minus;24.5, &ndash;28.1, &ndash;31.6, and &ndash;31.7 mm for methoxyflurane and &minus;14.6, &ndash;18.8, &ndash;19.2, and &ndash;23.7 mm for placebo, with a statistically significant treatment effect in favor of methoxyflurane overall across all four time points (&ndash;9.9 mm; 95% CI: &minus;17.4, &ndash;2.4 mm; P=0.0104). Median time to first pain relief was significantly shorter with methoxyflurane (1 minute) than placebo (3 minutes, P&lt;0.0001). Pain relief was reported within 1&ndash;10 inhalations in 95.7% of methoxyflurane-treated patients and 64.6% of placebo-treated patients. Rescue medication was requested by two (4.3%) methoxyflurane-treated patients and three (6.3%) placebo-treated patients. Over 95% of patients, physicians, and nurses rated methoxyflurane treatment as &ldquo;Excellent&rdquo;, &ldquo;Very Good&rdquo; or &ldquo;Good&rdquo; compared with between 64% and 68% for placebo. The incidence of adverse events was higher with methoxyflurane (51%) than placebo (42%), mostly comprising mild/transient dizziness and headache. Conclusion: This subgroup analysis shows that low-dose inhaled methoxyflurane is a rapid-acting and effective analgesic in adolescent patients presenting with moderate-to-severe trauma pain. Trial registration: Clinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12. Keywords: acute pain, analgesic, emergency department, injury, pediatric, Penthro

[Effect of cardiac embolism sources on origin of territorial cerebral infarcts].

BACKGROUND AND PURPOSE: To test the association of cardiac sources of embolism with territorial type brain infarcts. METHODS: From a prospective cerebral ischemia data base the 106 consecutive patients with territorial type cerebral infarcts on computerized tomography were analyzed. The 85 consecutive patients with lacunar lesions served as a comparison group. The association of cardiac sources of embolism with territorial types infarcts was assessed using univariate Chi Square tests and logistic regression models. Cardiac sources of embolism were defined as:atrial fibrillation, left cardiac thrombi, valvular vegetations, wall motion and valvular abnormalities, left atrial enlargement, open foramen ovale, septal aneurysm, mitral valve prolaps, and aortic arch atherothrombosis (all findings--except for atrial fibrillation--assessed by echocardiography). RESULTS: Atrial fibrillation was significantly associated with territorial type infarcts (odds ratio 2.2, 95% confidence interval 1.01-4.8). This effect was independent of additional cardiac diseases, other cardiac abnormalities, carotid artery stenosis, and patient age. Most likely due to the small sample size, left cardiac thrombi only showed a non-significant trend towards an association with territorial infarcts (odds ratio 3.0, 95% confidence interval 0.7-12.3). The rate of all other cardiac findings did not differ significantly between the comparison groups. CONCLUSION: Atrial fibrillation and cardiac thrombi showed an association with territorial type infarcts. Other so-called cardiac sources of embolism--except for mechanical valves and bacterial endocarditis which were not represented in our sample--revealed no clinically relevant association with embolic brain infarct pattern