Hemorrhage after Thrombolytic Therapy for Stroke: The Clinically Relevant Number Needed to Harm

The Journal of Emergency Medicine develop CFS at 6 months are physical inactivity, early positivity for heterophil antibody, and physical deconditioning 4 months earlier. There were no significant associations between CFS and any other immune response nor EBV load in mouth washings. The remainder of the editorial discusses a study in the same issue of the Journal of Infectious Diseases that examined gene expression over time in EBV-infected persons. The authors found 35 genes important in immune response and neuronal function that were abnormally expressed in those with prolonged, disabling fatigue. However, there was no obviously coherent pattern of function or consistent target tissue in these 35 genes. Although reasonably accurate soon after infection, no differentiation of gene expression between control subjects and cases at 6 months was possible by cluster analysis. [Benjamin Hatten, MD, Denver Health Medical Center, Denver, CO] Comments: This editorial serves as a brief overview of the relationship between CFS and infection. It highlights known risk factors and offers guidance for further study. Perhaps the most salient point is that CFS seems to be unrelated to mood disorders and is more closely linked to infection and activity level.

e HEMORRHAGE AFTER THROMBOLYTIC THERAPY FOR STROKE: THE CLINICALLY RELEVANT NUMBER NEEDED TO HARM. Saver JL. Stroke 2007;38: 2279 – 83. To assist medical providers and patients in making decisions about the use of tissue plasminogen activator (tPA) in the setting of acute ischemic stroke, the author set out to determine a more “clinically relevant” number needed to harm (NNTH) value for symptomatic intracerebral hemorrage (SICH) using the publicly available National Institute of Neurological Disorders and Stroke (NINDS) trials 1 and 2 data set. Based on the notion that the most “clinically relevant” outcome of stroke is final global function, a 15-variable prognostic model was derived from the NINDS data and used to predict outcome for patients with tPA-related SICH had they been treated with placebo rather than tPA and not experienced SICH. In the NINDS data, 20 of 312 patients treated with tPA developed SICH. Comparisons between the actual outcomes of the 20 patients developing SICH and the projected outcomes of these same 20 patients using the prognostic model were compared for final global functioning using the modified Rankin Scale (mRS). The NNTH for one more patient to have a final disabled or dead outcome (mRS ⱖ 3) attributable to tPA-related SICH was 707, with NNTH for worsened outcome by any degree across all levels of mRS for tPA reported as 29.7 to 40.1. This is compared to the originally reported number needed to treat with protocol-defined SICH (PDSICH) of 17.2, which is often reported as the NINDS data’s NNTH. In the discussion, the author suggests that many patients who experience SICH are destined for poor final global function despite treatment with tPA, based on the severity of their original injury, and that many do not have their final global outcome altered by SICH. In conclusion, the author proposes that the clinically relevant

445 NNTH numbers calculated from this article’s prognostic model demonstrate a more favorable benefit-risk ratio for NINDS criteria patients treated with tPA in the setting of acute ischemic stroke. [Todd Guth, MD, Denver Health Medical Center, Denver, CO] Comments: This article provides another complicated, retrospective avenue for drawing conclusions about the NINDS data. Limitations due to the number of patients contained in the database and the lack of consensus about the ultimate outcome measurements for stroke allow for continued debate about the use of thrombolytics in acute ischemic stroke. Clearly, this author thinks outcomes measured by final global disability demonstrate a favorable treatment, but additional research will be needed before consensus can be reached across disciplines.

e AORTIC PERFORATION WITH CARDIAC TAMPONADE TWO WEEKS AFTER PACEMAKER IMPLANTATION. Kalijusto M, Tønnessen T. J Thorac Cardiovasc Surg 2007;134:502–3. This case report from Norway relates to an uncommon presentation of aortic perforation with cardiac tamponade approximately 2 weeks after implantation of a cardiac pacemaker. A patient experienced an acute onset of chest pain with hemodynamic instability. A computed tomography scan demonstrated pericardial tamponade with type A aortic dissection secondary to posterior migration of a right atrial lead. Although epicardial perforation by pacemaker leads is a well-known complication of pacemaker placement, few have clinically serious outcomes unless there is a chamber rupture leading to cardiac tamponade, or considerably more significant and infrequent, an aortic perforation. [Andrew French, MD, Denver Health Medical Center, Denver, CO]

e DOES THIS CHILD HAVE APPENDICITIS? THE RATIONAL CLINICAL EXAMINATION. Bundy DG, Byerley JS, Liles EA, et al. JAMA 2007;298(4):438 –51. Appendicitis is the most frequent surgical etiology among children presenting to the Emergency Department or outpatient clinics with abdominal pain. The authors of this study conducted a literature review to assess the precision and accuracy of symptoms, signs, and laboratory results for evaluating children with a possible diagnosis of appendicitis. A literature search yielded 25 studies that provided primary data on children in whom the diagnosis of appendicitis was considered. There was only one study that included all children who presented with abdominal pain of less than 1 week duration, (assigned a quality level of 1); the prevalence of appendicitis was 10%. The 24 remaining studies included patients with a predetermined suspicion of appendicitis (all assigned a quality level of 3). Symptoms useful in the diagnosis of appendicitis included fever with a likelihood ratio (LR) of 3.4 and negative LR of 0.32 in the level 1 study (although less predictive in the