Random trials

A configurational Monte Carlo algorithm based on uniform random trial moves and the acceptance probability... 

Several clinical trials have been conducted with streptokinase adrninistered either intravenously or by direct infusion into a catheterized coronary artery. The results from 33 randomized trials conducted between 1959 and 1984 have been examined (75), and show a significant decrease in mortaUty rate (15.4%) in enzyme-treated patients vs matched controls (19.2%). These results correlate well with an ItaUan study encompassing 11,806 patients (76), in which the overall reduction in mortaUty was 19% in the streptokinase-treated group, ie, 1.5 million units adrninistered intravenously, compared with placebo-treated controls. The trial also shows that a delay in the initiation of treatment over six hours after the onset of symptoms nullifies any benefit from this type of thrombolytic therapy. Conversely, patients treated within one hour from the onset of symptoms had a remarkable decrease in mortaUty (47%). The benefits of streptokinase therapy, especially in the latter group of patients, was stiU evident in a one-year foUow-up (77). In addition to reducing mortahty rate, there was an improvement in left ventricular function and a reduction in the size of infarction. Thus early treatment with streptokinase is essential. 

Quinn, J., Wells, G., Sutcliffe, T., Jarmuske, M., Maw, J., Stiell, I. and Johns, P., A randomized trial comparing octylcyanoacrylate tissue adhesive and sutures in the management of... 

Malcolm R, Myrick H, Roberts J, et al The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med 17 349—355, 2002... 

O Connor PG, Carroll KM, Shi JM, et al Three methods of opioid detoxification in a primary care setting a randomized trial. Ann Intern Med 127 526-530, 1997 Oppenheimer E, Tobutt C, Taylor C, et al Death and survival in a cohort of heroin addicts from London clinics a 22-year follow-up study Addiction 89 1299—1308, 1994... 

Dennis M, Babor TF, Roebuck C, et al Changing the focus the case for recognizing and treating cannabis use disorders. Addiction 97(suppl 1) 4—15, 2003 Dennis M, Godley SH, Diamond G, et al The Cannabis Youth Treatment (CYT) Study main findings from two randomized trials. J Subst Abuse Treat 27 197— 213, 2004... 

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

Oncken CA, Hatsukami DK, Lupo VR, et al Effects of short-term use of nicotine gum in pregnant smokers. Clin Pharmacol Ther 59 654-61, 1996 Pomerleau OF, Pomerleau CS Neuroregulators and the reinforcement of smoking towards a biobehavioral explanation. Neurosci Biobehav Rev 8 503—513, 1984 Prochazka AV, Weaver MJ, Keller RT, et al A randomized trial of nortriptyline for smoking cessation. Arch Intern Med 158 2035-2039, 1998 Puska P, Korhonen HJ, Vartiainen E, et al Combined use of nicotine patch and gum compared with gum alone in smoking cessation a clinical trial in North Karelia. Tob Control 4 231-235, 1995... 

CanbakanB, SenturkH, TabakF, Akdogan M, Tahan V, Mert A, Sut N, Ozaras R, Midilli K, Ozbay G (2006) Efficacy of interferon alpha-2b and lamivudine combination treatment in comparison to interferon alpha-2b alone in chronic delta hepatitis a randomized trial. J Gastroenterol Hepatol 21 657-663... 

Elewski B, Fleischer AB, Pariser DM (2003) A comparison of 15% topical azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papu-lopustular facial rosacea results of a randomized trial. Arch Dermatol 139 1444-1450... 

The effect of drug concentration expression on epinephrine dosing errors a randomized trial. Ann 37 Intern Med 2008 148 11-14. 

Guendelman S, Meade K, Benson M, et al. Improving asthma outcomes and selfmanagement behaviors of inner-city children a randomized trial of the Health... 

Kieburtz K, Simpson D et al (1998) A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team. Neurology... 

Three large randomized trials, the European Cooperative Acute Stroke Study (ECASS) parts I and II, and the Alteplase Thrombolysis for Acute Noninterven-tional Therapy in Ischemic Stroke (ATLANTIS), have investigated the efficacy of IV rt-PA in acute stroke beyond the 3-hour window. All three studies showed high rates of sICH complicating rt-PA treatment, and no overall efficacy of rt-PA. 

There have been three large randomized trials of streptokinase in acute ischemic stroke treatment, all of which were terminated early because of increased sICH and mortality in the treatment group (Table 3.1)." " " ... 

IV rt-PA has been safely given in patients with cervical arterial dissection There are four reports of IV rt-PA use in pregnancy, with one case complicated by intrauterine hematoma,rt-PA should be used in this setting only after careful assessment of the risks and benefits. There is insufficient data to determine the benefit of rt-PA in the pediatric population, with no randomized trials. 

The Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic rt-PA (CLOTBUST) study was a phase II randomized trial which compared continuous transcranial Doppler ultrasound insonation, in subjects with ultrasound evidence of MCA occlusion being given IV rt-PA, to sham insona-tion. ° There was an increased rate of arterial recanalization with the continuous insonation (49% vs. 30%, p = 0.03) and no increased risk of sICH. 

The RANTTAS Investigators. A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). Stroke 1996 27 447-453. 

HilUs AE, Ulatowski JA, Barker PB, Torbey M, Ziai W, Beauchamp NJ, Oh S, Wityk RJ. A pilot randomized trial of induced blood pressure elevation effects on function and focal perfusion in acute and subacute stroke. Cerebrovasc Dis 2003 16 236-246. 

Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. The EC/IC Bypass Study Group. N Engl J Med 1985 313 1191-1200. 

One meta-analysis examined the safety and efficacy of LMWH and heparinoids in 11 randomized trials of 3048 patients with acute ischemic stroke. It reported a reduction in the incidence of deep venous thrombosis (DVT) (odds ratio (OR) 0.27,... 

The Heparin in Acute Embolic Stroke Trial (HAEST) was a multicenter, randomized trial of the effect of LMWH (dalteparin 100 lU/kg sc twice daily) or aspirin (160 mg once daily) for the acute treatment of 449 patients with ischemic stroke and atrial fibrillation (AF). The primary outcome was the rate of recurrent stroke within 14 days. No difference in rates of early recurrence (8.5% dalteparin treated vs. 7.5% aspirin treated) or good 3-month functional outcome was found. The frequency of early slCH was 2.7% on dalteparin versus 1.8% on aspirin. 

PROFESS is an ongoing large randomized trial examining combination ER-DP plus aspirin therapy compared with clopidogrel (each group also with or without telmisartan, an angiotensin receptor antagonist) for the secondary prevention of early and late recurrent stroke, and other vascular events. 

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