Both methylphenidate and placebo resulted in significant symptom improvement. Methylphenidate was not significantly superior to placebo after 1 week of treatment. Longer study duration is justified. The role of daily telephone calls from a research nurse should be explored as a palliative care intervention.

These preliminary results suggest that patient-controlled methylphenidate administration rapidly improved fatigue and other symptoms. Randomized controlled trials are justified.

Background and Purpose-Argatroban is a direct thrombin inhibitor that safely augments recanalization achieved by tissue-type plasminogen activator (tPA) in animal stroke models. The Argatroban tPA Stroke Study was an open-label, pilot safety study of tPA plus Argatroban in patients with ischemic stroke due to proximal intracranial occlusion. Methods-During standard-dose intravenous tPA, a 100-g/kg bolus of Argatroban and infusion for 48 hours was adjusted to a target partial thromboplastin time of 1.75ϫ baseline. The primary outcome was incidence of significant intracerebral hemorrhage defined as either symptomatic intracerebral hemorrhage or Parenchymal Hematoma Type 2. Recanalization was measured at 2 and 24 hours by transcranial Doppler or CT angiography. Results-Sixty-five patients were enrolled (45% men, mean age 63Ϯ14 years, median National Institutes of Health Stroke Scaleϭ13). The median (interquartile range) time tPA to Argatroban bolus was 51 (38 -60) minutes. Target anticoagulation was reached at a median (interquartile range) of 3 (2-7) hours. Significant intracerebral hemorrhage occurred in 4 patients (6.2%; 95% CI, 1.7-15.0). Of these, 3 were symptomatic (4.6%; 95% CI, 0.9 -12.9). Seven patients (10%) died in the first 7 days. Within the 2-hour monitoring period, transcranial Doppler recanalization (nϭ47) occurred in 29 (61%) patients: complete in 19 (40%) and partial in another 10 (21%). Conclusions-The combination of Argatroban and intravenous tPA is potentially safe in patients with moderate neurological deficits due to proximal intracranial arterial occlusions and may produce more complete recanalization than tPA alone. T he thrombin inhibitor Argatroban (GlaxoSmithKline, Philadelphia, PA) selectively inhibits free and clotassociated thrombin. 1,2 Safety has been demonstrated with and without thrombolytics or with aspirin in patients with acute myocardial infarction. [3][4][5] In a randomized trial of Argatroban versus heparin in combination with intravenous thrombolysis for acute myocardial infarction, complete coronary reperfusion was significantly more frequent with Argatroban compared with heparin. 3 In animal stroke models, Argatroban safely augments the benefit of recombinant tissue-type plasminogen activator (tPA) by improving microcirculatory flow, increasing speed and completeness of recanalization, and preventing reocclusion. 6 -10 Argatroban monotherapy (in a double-blind, randomized Phase II trial) in 60 patients with stroke within 48 hours of onset improved The benefit of tPA in acute stroke is linked to the speed and degree of clot lysis and artery recanalization. 16 -18 However, only 20% to 30% of patients will have complete recanalization on transcranial Doppler imaging (TCD) within 2 hours of intravenous tPA therapy, 60% will have only partial recanalization, and 34% of those with any recanalization will experience reocclusion. 19,20 Because of its short half-life, allowing careful titration of the anticoagulant effect, we hypothesized that Argatroban might be safely added to...

The purpose of this study was to determine the impact of physician sitting versus standing on the patient's preference of physician communication style, and perception of compassion and consult duration. Sixty-nine patients were randomized to watch one of two videos in which the physician was standing and then sitting (video A) or sitting and then standing (video B) during an inpatient consultation. Both video sequences lasted 9.5 minutes. Thirty-five patients (51%) blindly preferred the sitting physician, 16 (23%) preferred the standing, and 18 (26%) had no preference. Patients perceived that their preferred physician was more compassionate and spent more time with the patient when compared with the other physician. There was a strong period effect favoring the second sequence within the video. The patients blinded choice of preference (P = 0.003), perception of compassion (P = 0.0016), and other attributes favored the second sequence seen in the video. The significant period effect suggests that patients prefer the second option presented, notwithstanding a stated preference for a sitting posture (55/68, 81%). Physicians should ask patients for their preference regarding physician sitting or standing as a way to enhance communication.

Donepezil was not significantly superior to placebo in the treatment of cancer-related fatigue.

RATIONALE : Preclinical work demonstrates that the transcription factor peroxisome proliferator-activated receptor gamma plays an important role in augmenting phagocytosis while modulating oxidative stress and inflammation. We propose that targeted stimulation of phagocytosis to promote efficient removal of the hematoma without harming surrounding brain cells may be a therapeutic option for intracerebral hemorrhage. AIMS : The primary objective is to assess the safety of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in increasing doses for three-days followed by a maintenance dose, when administered to patients with spontaneous intracerebral hemorrhage within 24 h of symptom onset compared with standard care. We will determine the maximum tolerated dose of pioglitazone. STUDY DESIGN : This is a prospective, randomized, blinded, placebo-controlled, dose-escalation safety trial in which patients with spontaneous intracerebral hemorrhage are randomly allocated to placebo or treatment. The Continual Reassessment Method for dose finding is used to determine the maximum tolerated dose of pioglitazone. Hematoma and edema resolution is evaluated with serial magnetic resonance imaging (MRI) at specified time points. Functional outcome will be evaluated at three- and six-months. OUTCOMES : The primary safety outcome is mortality at discharge. Secondary safety outcomes include mortality at three-months and six-months, symptomatic cerebral edema, clinically significant congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Radiographic outcomes will explore the time frame for resolution of 25%, 50%, and 75% of the hematoma. Clinical outcomes are measured by the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, modified Rankin Scale, Stroke Impact Scale-16, and EuroQol at three- and six-months.

Background and Purpose We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to rt-PA treated ischemic stroke patients. Methods Patients treated with standard-dose rt-PA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100-μg/kg bolus) followed by infusion of either 1 μg/kg/min (low-dose) or 3 μg/kg/min (high-dose) for 48 hours. Safety was incidence of symptomatic intracerebral hemorrhage (sICH). Probability of clinical benefit (mRS 0–1 at 90-days) was estimated using a conservative Bayesian Poisson model (neutral prior probability centered at relative risk [RR]=1.0 and 95% prior intervals: 0.33–3.0). Results Ninety patients were randomized: 29 to rt-PA alone, 30 to rt-PA + low-dose argatroban, and 31 to rt-PA + high-dose argatroban. Rates of sICH were similar among control, low-dose and high-dose arms: 3/29 (10%); 4/30 (13%); and 2/31 (7%), respectively. At 90-days 6 (21%) rt-PA alone; 9 (30%) low-dose, and 10 (32%) high-dose patients were mRS 0–1. The RR (95% Credible Interval) for mRS 0–1 with low, high, and either low or high dose argatroban was 1.17 (0.57, 2.37), 1.27 (0.63, 2.53), and 1.34 (0.68, 2.76). The probability that adjunctive argatroban was superior to rt-PA alone was 67%, 74%, and 79% for low, high, and low or high dose, respectively. Conclusions In patients treated with rt-PA, adjunctive argatroban was not associated with increased risk of sICH and provides evidence that a definitive effectiveness trial is indicated.

Awareness of the association between S-3 nerve root resection and bowel and bladder incontinence may help surgeons' decision-making process.