Blinded Endpoint Assessment Research Articles

A Randomized Trial of a Physical Conditioning Program to Enhance the Driving Performance of Older Persons

BackgroundAs the number of older drivers increases, concern has been raised about the potential safety implications. Flexibility, coordination, and speed of movement have been associated with older drivers’ on road performance.ObjectiveTo determine whether a multicomponent physical conditioning program targeted to axial and extremity flexibility, coordination, and speed of movement could improve driving performance among older drivers.DesignRandomized controlled trial with blinded assignment and end point assessment. Participants randomized to intervention underwent graduated exercises; controls received home, environment safety modules.ParticipantsDrivers, 178, age ≥ 70 years with physical, but without substantial visual (acuity 20/40 or better) or cognitive (Mini Mental State Examination score ≥24) impairments were recruited from clinics and community sources.MeasurementsOn-road driving performance assessed by experienced evaluators in dual-brake equipped vehicle in urban, residential, and highway traffic. Performance rated three ways: (1) 36-item scale evaluating driving maneuvers and traffic situations; (2) evaluator’s overall rating; and (3) critical errors committed. Driving performance reassessed at 3 months by evaluator blinded to treatment group.ResultsLeast squares mean change in road test scores at 3 months compared to baseline was 2.43 points higher in intervention than control participants (P = .03). Intervention drivers committed 37% fewer critical errors (P = .08); there were no significant differences in evaluator’s overall ratings (P = .29). No injuries were reported, and complaints of pain were rare.ConclusionsThis safe, well-tolerated intervention maintained driving performance, while controls declined during the study period. Having interventions that can maintain or enhance driving performance may allow clinician–patient discussions about driving to adopt a more positive tone, rather than focusing on driving limitation or cessation.

The Rapid Anticoagulation Prevents Ischemic Damage Study in Acute Stroke – Final Results from the Writing Committee

metric tests were used as appropriate. Thirty months after the onset of the study, recruitment was closed after 67 patients had been recruited, emphasizing the diffi culties of academic trials to recruit centers and patients without adequate funding, regardless of the clinical relevance of the question addressed. As illustrated in table 1 , there were close similarities between the 2 treatment groups, although a higher proportion of patients allocated to UH had large infarctions at baseline CT scan. As shown In the rat ischemic brain, unfractionated heparin (UH) is neuroprotective [1] , although its clinical value in acute stroke is still a matter of controversy [2–10] . The Rapid Anticoagulation Prevents Ischemic Damage (RAPID) Trial compared the value of aspirin and UH in patients with suspected nonlacunar ischemic stroke and symptoms lasting less than 12 h using a parallel group, randomized, open, blinded endpoint assessment (PROBE) design. A brain CT scan was mandatory at baseline to exclude any amount of blood, and patients or proxies signed an informed written consent. UH was started with an intravenous bolus of 40 IU/kg of UH followed by a weight-adjusted continuous infusion of 12 IU/kg/h aimed to achieve UH plasma levels of 0.3–0.5 U/ml as soon as possible. Control of UH therapy was assessed with aPTT ratios (patient aPTT/ control aPTT). Six hours after treatment onset, or after any dose adjustment, an aPTT was obtained. Otherwise, aPTTs were ordered every 12 h. Local laboratories were requested at study onset to calibrate the aPTT ratio to their corresponding UH levels. Aspirin (300 mg/day) was given orally or by nasogastric tube. The study treatment was maintained for 6 8 1 days in stroke units of tertiary hospitals. The primary endpoint of the RAPID study was the rate of favorable outcome defi ned as a modifi ed Rankin scale ^ 2 at day 90 8 14 days. The modifi ed Rankin scale was centrally assessed by telephone interview by investigators blind to treatment allocation. The main secondary endpoints included the single and combined incidence of recurrent stroke (appearance of new symptoms), worsening stroke (at least 4 points change in NIHSS score), symptomatic intracerebral hemorrhage, systemic bleeding, deep venous thrombosis, pulmonary embolism and death at day 90. A Steering Committee and a DSMB directed and supervised the study. All centers had the approval of an independent ethics committee. For sample size calculations, 592 patients per treatment group were required ( � 0.05%, � 80%) to detect or disprove an absolute difference of about 8% in favorable outcome. Parametric and nonpara

Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial of cardiovascular events in high-risk hypertensive patients: rationale, design, and methods.

Hypertension continues to be a major public health issue in the world. To combat this problem, many anti-hypertensive drugs have been developed and proven effective at controlling blood pressure in the last half century. In recent decades, antihypertensive drugs have been shown to have cardiovascular benefits beyond the reduction of blood pressure, and the focus has shifted to clarification of these effects. Angiotensin II receptor antagonists and calcium channel blockers are the most widely used antihypertensive drugs in Japan. However, these two classes of drugs have not yet been compared with respect to their efficacy for treating cardiovascular events. The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial described herein is a prospective, multicenter, randomized, open-label, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration and blinded assessment of endpoints in high-risk hypertensive patients treated with either an angiotensin II receptor antagonist (candesartan cilexetil) or a third-generation calcium channel blocker (amlodipine besilate). The eligibility criteria in this study were 1) age between 20 and 85 years; 2) systolic blood pressure (SBP) > or = 140 mmHg in those below 70 years of age or > or = 160 mmHg in those above 70 years of age or diastolic blood pressure (DBP) > or = 90 mmHg on two consecutive measurements at clinic; and 3) at least one of the following high risk factors for cardiovascular events: a) SBP > or = 2180 mmHg or DBP > or = 110 mmHg on two consecutive visits, b) type 2 diabetes mellitus (fasting blood glucose > or = 126 mg/dl, casual blood glucose > or = 200 mg/dl, HbA1c > or = 6.5%, 2 h blood glucose on 75 g oral glucose tolerance test (OGTT) > or = 200 mg/dl, or current treatment with hypoglycemic therapy), c) history of cerebral hemorrhage, cerebral infarction, or transient ischemic attack until 6 months prior to the screening, d) left ventricular hypertrophy on either echocardiography or ECG, angina pectoris, or history of myocardial infarction until 6 months prior to screening, e) proteinuria or serum creatinine > or = 1.3 mg/dl, and f) symptoms of arteriosclerotic artery obstruction. The therapeutic goals of blood pressure control were set as follows: SBP < 130 mmHg and DBP < 85 mmHg for patients below 60 years of age, SBP < 140 mmHg and DBP < 90 mmHg for those in their 60s, SBP < 150 mmHg and DBP < 90 mmHg for those in their 70s, and SBP < 160 mmHg and DBP < 90 mmHg for those in their 80s. A total of 3,200 patients, equally allocated to each of the two treatment arms, were required based on a two-sided alpha level 0.05 and 90% power. The CASE-J is also the first study to employ the newly developed Automatic Bar Code Data-Capturing/Allocation, Booking & Trial Coding, Data Management (ABCD) system for data collection and management. Enrollment of patients started in September 2001 and ended in December 2002. Follow-up data will be collected every 6 months until December 2005. The CASE-J trial will provide important evidence on the comparative effectiveness of candesartan cilexetil and amlodipine besilate on cardiovascular morbidity and mortality among Japanese. In addition, the use of the ABCD system is expected to contribute to the development of more efficient data management systems for large-scale clinical trials.