Derivation and validation of a sensitive IMA cutpoint to predict cardiac events in patients with chest pain.

OBJECTIVES: In patients with acute chest pain, we derived a cutpoint for ischaemia-modified albumin (IMA) and prospectively validated this cutpoint to predict 30-day major adverse cardiac events (MACEs). METHODS: We prospectively recruited a derivation cohort (18-month period) to establish a serum IMA cutpoint targeting 80% sensitivity. This was followed by a prospective validation cohort study of emergency department patients with acute chest pain at two university hospitals over a 3-month period. A MACE was defined as myocardial infarction, revascularisation or death at 30-day follow-up. RESULTS: In the derivation cohort of 151 patients, the IMA cutpoint that achieved 80% sensitivity for MACEs was 75 KU/litre. The sensitivity was prospectively validated in 171 patients consecutively enrolled, of whom 106 underwent multiple-biomarker analysis (19.8% MACE rate, 81% sensitivity of IMA). Furthermore, IMA by itself (81%, p<0.01) and in combination with initial highly sensitive cardiac troponin T (hsTnT) (90%, p<0.001) had significantly higher sensitivity than initial hsTnT (29%) for prediction of MACEs. CONCLUSIONS: We prospectively validated the sensitive IMA cutpoint of 75 KU/litre with 80% sensitivity for MACEs in patients with acute chest pain. Our data suggest that IMA alone and in combination with initial hsTnT are more sensitive than the initial hsTnT for MACEs.

Masticatory stress, orbital orientation and the evolution of the primate postorbital bar.

A postorbital bar is one of a suite of derived features which distinguishes basal primates from their putative sister taxon, plesiadapiforms. Two hypotheses have been put forward to explain postorbital bar development and variation in circumorbital form: the facial torsion model and visual predation hypothesis. To test the facial torsion model, we employ strain data on circumorbital and mandibular loading patterns in representative primates with a postorbital bar and masticatory apparatus similar to basal primates. To examine the visual predation hypothesis, we employ metric data on orbit orientation in Paleocene and Eocene primates, as well as several clades of visual predators and foragers that vary interspecifically in postorbital bar formation.A comparison of galago circumorbital and mandibular peak strains during powerful mastication demonstrates that circumorbital strains are quite low. This indicates that, as in anthropoids, the strepsirhine circumorbital region is excessively overbuilt for countering routine masticatory loads. The fact that circumorbital peak-strain levels are uniformly low in both primate suborders undermines any model which posits that masticatory stresses are determinants of circumorbital form, function and evolution. This is interpreted to mean that sufficient cortical bone must exist to prevent structural failure due to non-masticatory traumatic forces. Preliminary data also indicate that the difference between circumorbital and mandibular strains is greater in larger taxa.Comparative analyses of several extant analogs suggest that the postorbital bar apparently provides rigidity to the lateral orbital margins to ensure a high level of visual acuity during chewing and biting. The origin of the primate postorbital bar is linked to changes in orbital convergence and frontation at smaller sizes due to nocturnal visual predation and increased encephalization. By incorporating in vivo and fossil data, we reformulate the visual predation hypothesis of primate origins and thus offer new insights into major adaptive transformations in the primate skull.

Preemptive epidural analgesia and recovery from radical prostatectomy: a randomized controlled trial.

CONTEXT: Preemptive analgesia can decrease the sensitization of the central nervous system that would ordinarily amplify subsequent nociceptive input, but a clear demonstration of its clinical efficacy is necessary for it to become a routine component of acute pain therapy. OBJECTIVE: To determine the impact of preemptive epidural analgesia on postoperative pain and other clinically important outcome variables after radical retropubic prostatectomy. DESIGN AND SETTING: A block randomized double-blind clinical trial lasting 20 months at a single academic medical center. PATIENTS: A total of 100 generally healthy and neurologically intact patients scheduled for radical retropubic prostatectomy for the treatment of prostate cancer in whom an epidural catheter for treating postoperative pain was to be placed prior to the induction of general anesthesia. INTERVENTIONS: Epidural bupivacaine, epidural fentanyl, or no epidural drug was administered prior to induction of anesthesia and throughout the entire operation, followed by aggressive postoperative epidural analgesia for all patients. MAIN OUTCOME MEASURES: Daily pain scores during hospitalization and pain scores obtained 3.5, 5.5, and 9.5 weeks after hospital discharge. RESULTS: The patients who received epidural fentanyl or bupivacaine prior to surgical incision (preemptive analgesia) experienced 33% less pain while hospitalized (P=.007). Pain scores in those receiving preemptive analgesia were significantly lower at 9.5 weeks (P=.02), but were not significantly different at 3.5 or 5.5 weeks. At 9.5 weeks, 32 (86%) of 37 patients receiving preemptive analgesia were pain-free compared with 9 (47%) of 19 control patients (P=.004). Patients receiving preemptive analgesia were more active 3.5 weeks after surgery (P=.01), but not at 5.5 or 9.5 weeks. CONCLUSIONS: Even in the presence of aggressive postoperative pain management, preemptive epidural analgesia significantly decreases postoperative pain during hospitalization and long after discharge, and is associated with increased activity levels after discharge.