Outcomes clinical

The treatment of an autoimmune disease very much depends on the nature of the clinical outcome it causes. Although the formation of autoantibodies causes the inactivation of the gastric intrinsic factor, the subsequent shortage of vitamin B12 can be easily overcome by supplying it via an parenteral route. Lifelong immunosuppression (with all its side effects) thus is inappropriate. When, however, as in sympathetic ophtalmia, after damage of the first eye the second eye is endangered, an even drastic immunosuppression is mandatory. 

Substrate Inhibitor Inhibited enzyme Possible clinical outcome... 

Although in vitro models clearly show that MDR transporters can protect tumor cells, their relevance in clinical oncology remains controver sial. As is the case for most potentially useful cancer biomarkers, no universally embraced guidelines for analytical or clinical validation of MDR transporters exist. Evidence linking ABCB1 Pgp/MDRl expression with poor clinical outcome is most conclusive for breast cancer, sarcoma, and certain types of leukemia. The relevance of the other MDR transporters in clinical MDR is still unclear. The prognostic implication of ABCCl/ MRPl remains controversial and very little is known clinically about ABCG2. 

The measurement of ER has become a standard assay in the clinical management of breast cancer. The presence of ERa identifies those breast cancer patients with a lower risk of relapse and better clinical outcome. Receptor status also provides a guideline for those tumors that may be responsive to hormonal intervention. But only about half of ER-positive patients respond to hormonal therapies. Of those who respond initially, most will eventually develop an estrogen unresponsive disease following a period of treatment even though ERa is often still present. Mutant receptors and constitutively active r eceptors as well as hormone-independent activation of the ERa are discussed. The involvement of ER 3 isoforms is under investigation. 

Rickels K, Case WG, Downing RW, et al Long-term diazepam therapy and clinical outcome. JAMA 230 767-771, 1983... 

Clinical outcome, work status, Conference poster... 

Finley PR, Sommer BR, Corbitt JL, et al (1998). Risperidone clinical outcome predictors and cost-effectiveness in a naturalistic setting. PsychopharmacolBull b y 75-81. 

In support of this, several recent studies have evaluated the clinical outcomes observed in flavivirus-infected patients that carry the CCR5A32 allele. One group... 

Beaulieu C, de Crespigny A, Tong DC, Moseley ME, Alhers GW, Marks MP. Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke evolution of lesion volume and correlation with clinical outcome. Arm Neurol 1999 46 568-578. 

Lev MH, Segal AZ, Farkas J, Hossain ST, Putman C, Hunter GJ, Budzik R, Harris GJ, Buonanno FS, Ezzeddine MA, Chang Y, Koroshetz WJ, Gonzalez RG, Schwamm LH. Utility of perfusion-weighted CT imaging in acute middle cerebral artery stroke treated with intra-arterial thrombolysis prediction of final infarct volume and clinical outcome. Stroke 2001 32 2021-2028. 

Coutts SB, Lev MH, Eliasziw M, Roccatagliata L, Hill MD, Schwamm LH, Pexman JH, Koroshetz WJ, Hudon ME, Buchan AM, Gonzalez RG, Demchuk AM. ASPECTS on CTA source images versus unenhanced CT added value in predicting final infarct extent and clinical outcome. Stroke 2004 35 2472-2476. 

The PRO ACT-11 trial was designed to assess the clinical efficacy and safety of lA r-pro-UK. In this study, 180 patients were enrolled in a 2 1 randomization scheme to receive either 9 mg lA r-pro-UK plus 4 hours of low-dose IV heparin, or low-dose IV heparin alone. The primary clinical outcome, the proportion of patients with slight or no disability at 90 days (mRS of < 2), was achieved in 40% of the 121 patients in the r-pro-UK treatment group, compared to 25% of the 59 patients in the control group (absolute benefit 15%, relative benefit 58%, number need to treat = 7 p = 0.04). The recanalization rate (TlMl 2 and 3) was 66% for the r-pro-UK group and 18% for the control group (p < 0.001). Symptomatic ICH within 24 hours occurred in 10% of r-pro-UK patients and 2% of control patients (p = 0.06). All symptomatic ICHs occurred in patients with a baseline NIHSS... 

Internal Carotid Artery Occlusion Acute stroke due to a distal ICA T (T = terminus) occlusion carry a much worse prognosis than MCA occlusions. In a recent analysis of 24 consecutive patients (median NIHSS 19) presenting with T occlusions of the ICA who were treated by lAT using urokinase at an average of 237 minutes from symptom onset, only four patients (16.6%) had a favorable outcome at 3 months. Partial recanalization of the intracranial ICA was achieved in 15 (63%), of the MCA in 4 (17%), and of the ACA in 8 patients (33%). Complete recanalization did not occur. The presence of good leptomeningeal collaterals and age <60 years were the only predictors of a favorable clinical outcome. New treatment strategies, such as the combination of IV rt-PA and lAT, or the use of new mechanical devices may improve the outcome in these patients. 

No direct comparison trials have been reported between the different thrombolytic agents in acute ischemic stroke. In a retrospective review of the results for acute stroke lAT performed at our center, we have found significantly higher rates of recanalization and good clinical outcome in the era in which lA UK was used versus the era in which UK was not available and lAT with rt-PA was the primary treatment. Conversely, in another retrospective study, Eckert et al. found no major difference between the recanalization rates of UK and rt-PA. 

Saver JL. Number needed to treat estimates incorporating effects over the entire range of clinical outcomes novel derivation method and application to thrombolytic therapy for acute stroke. Arch Neurol 2004 61 1066-1070. 

Anakinra/Kineret, an IL-1 receptor antagonist approved for use in rheumatoid arthritis, was recently evaluated in a small phase II trial. When initiated within 6 hours after stroke onset, Anakinra treatment yielded promising preliminary results it was deemed safe with demonstrable biologic activity and likely favorable clinical outcome." ... 

FIGURE 5.2 Clinical outcome of patients in the double-blind, proof-of-concept trial evaluating EPO in acute stroke, (a) Barthel Index (rhEPO vs. placebo, p < 0.05). (b) Modified Rankin Scale (rhEPO vs. placebo, p < 0.07) on day 30. Dead patients received the worst possible score. Evolution of lesion size of patients in the efficacy trial of Albumin in acute stroke, ((a-1) and DWI and (a-2) FLAIR.) (Reprinted with permission from reference 50.)... 

Jonsson N, Asplund K. Does pretreatment with statins improve clinical outcome after stroke A pilot case-referent study. Stroke 2001 32 1112-1115. 

Leonhardt G, Wilhelm H, Doerfler A, Ehrenfeld CE, Schoch B, Rauhut F, Hufnagel A, Diener HC. Clinical outcome and neuropsychological deficits after right decompressive hemicraniectomy in mca infarction. J Neurol 2002 249 1433-1440. 

The same investigators found significant improvements in clinical outcomes and reduction in ischemic lesion volumes on MRI in 13 patients treated with tirofiban and reduced-dose rt-PA compared to 16 patients treated with standard rt-PA therapy. ... 

De Georgia et al. Stroke 2004 63 312-317 Prospective, randomized cooling vs. standard therapy for feasibility and safety 18 of40tx with hypothermia Hypothermia to 33°C with endovascular catheter on safety in pts with anterior circulation stroke and NIHSS >8 Similar clinical outcomes and lesion growth as measured on DWI MRI. Nonsignificant reduction in DWI volume in patients who cooled well. 

Because the severity of the vascular lesion contributes to the size of the infarction and thus the clinical outcome, CTA results may be expected to predict outcome. One study assessed the utihty of CTA in 40 patients with acute stroke syndromes and an NIHSS score of >8. The extent of leptomeningeal collaterals on CTA correlated with the outcome from thrombolysis. In 40 hyperacute stroke patients who received rt-PA, those with CTA evidence of poor collaterals, autolysed thrombi, and T lesions showed little benefit from treatment. ... 

Current data suggest little benefit on clinical outcomes beyond symptom relief for calcium channel blockers in the setting of ACS.43 Moreover, the use of first-generation shortacting dihydropyridines, such as nifedipine, should be avoided because they appear to worsen outcomes through their negative inotropic effects, induction of reflex sympathetic activation, tachycardia, and increased myocardial ischemia.43 Therefore, calcium channel blockers should be avoided in the acute management of MI unless there is a clear symptomatic need or a contraindication to p-blockers. 

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