Discrepancies in identification of bleeding events after percutaneous coronary intervention

STUDY OBJECTIVE: To evaluate the level of agreement between two sets of criteria, the Thrombolysis in Myocardial Infarction (TIMI) criteria and investigator-developed criteria, for identifying bleeding events in patients who had undergone a percutaneous coronary intervention (PCI) and to measure length of hospital stay (LOS) as a surrogate marker of bleeding severity. DESIGN: Retrospective chart review. SETTING: Two university-affiliated medical centers. PATIENTS: Four hundred twenty-two consecutive patients who had undergone PCI from December 1, 2001-June 30, 2002. MEASUREMENTS AND MAIN RESULTS: Data were collected on the number of bleeding events that occurred within 1 week after PCI (limited to one event/patient) and on LOS. Bleeding was assessed by TIMI criteria and by investigator-developed criteria. Bleeding according to TIMI criteria included intracranial hemorrhage, spontaneous hematuria or hematemesis, or decreases in hemoglobin level. Bleeding according to investigator-developed criteria included intracranial, retroperitoneal, intraocular, or clinically overt bleeding without a specified decrease in hemoglobin level. Agreement between criteria was assessed by means of the kappa statistic. Of the 422 patients, 23 (5%) experienced TIMI-defined bleeding events and 229 (54%) investigator-defined bleeding events. A kappa value of 0.09 (95% confidence interval 0.06-0.13) indicated a poor level of agreement between the two sets of bleeding criteria. The effect of this discrepancy on LOS was 66 fewer days of care when TIMI criteria were applied versus investigator-developed criteria in the 206 patients who experienced bleeding events that met investigator criteria (total LOS 645 days) but not TIMI criteria (total LOS 579 days). CONCLUSION: Bleeding assessment with use of TIMI criteria versus investigator-developed criteria yielded discrepant bleeding event rates and LOS, making it difficult to accurately compare bleeding rates and consequences across clinical trials and in practice. Consensus bleeding criteria are needed for applications in clinical evaluations of antithrombotic agents.     

Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke,seizures and sensorimotor gating deficit

Background and purpose:

Abnormal glutamatergic activity is implicated in neurologic and neuropsychiatric disorders. Selective glutamate receptor antagonists were highly effective in animal models of stroke and seizures but failed in further clinical development because of serious side effects, including an almost complete set of symptoms of schizophrenia. Therefore, the novel polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was studied in rat models of stroke, seizures and sensorimotor gating deficit.

Experimental approach:

3,5-DBr-L-Phe was administered intraperitoneally as three boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse inhibition (PPI) of startle (sensorimotor gating deficit).

Key results:

Brain damage caused by ET-1 was reduced by 52%, which is comparable with the effects of MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced seizures induced by PTZ without the significant effects on arterial blood pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe prevented the disruption of PPI measured 3 days after the administration of ET-1. 3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801.

Conclusion and implications:

The pharmacological profile of 3,5-DBr-L-Phe might be beneficial not only for developing a therapy for the neurological and cognitive symptoms of stroke and seizures but also for some neuropsychiatric disorders.     

The antiemetic action of propofol

Eighty patients who underwent minor gynaecological surgery were anaesthetised with either incremental propofol or incremental methohexitone after an opioid premedication. The group anaesthetised with propofol had significantly fewer emetic sequelae and the results suggest that propofol has a definite antiemetic action.     

Interpersonal guilt and the working alliance in psychotherapy: The moderating role of childhood experience

Interpersonal guilt often encompasses pathogenic beliefs that imply omnipotent responsibility for others and concerns about abandoning, humiliating or threatening others. This study sought to examine how interpersonal guilt may influence patients' and therapists' ratings of early working alliance and the potential moderating effect of perceived adverse parenting in childhood. Ninety-five patients and their 19 therapists in an outpatient psychotherapy clinic rated their early working alliance after the first and the fifth session in treatment. We conducted separate moderation analyses for patient and therapist-reported working alliance and controlled for psychological distress at baseline. Results suggest that perceived adverse parenting in childhood significantly moderated the effect of interpersonal guilt on the working alliance in such a way that for patients reporting very low levels of perceived adverse experiences, the interpersonal guilt beliefs had a positive effect on working alliance, whereas for those with very high levels of perceived adverse experiences, interpersonal guilt had a negative effect on working alliance. This same pattern of moderation was found for patient- and therapist-reported working alliance at session 1 and therapist-reported working alliance at session 5. Thus, although the effect of interpersonal guilt on the working alliance depends somewhat on the perspective of the working alliance rating (patient or therapist), it mainly depends on developmental experiences of the patient.